Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline

In the paper

“Serum T3 or free T3 (fT3) levels are generally not helpful in diagnosing CH; most patients with CH have low fT3 levels, but there is considerable overlap between CH and non-CH patients with pituitary MAY 4, 2016 disease (75,77).”

What the sources say

• ?Could not verify

  The Background and Results discuss steroid hormone immunoassays, not T3 or free T3 testing. Searches for free T3, hypothyroidism, and pituitary disease found no passage addressing whether fT3 helps diagnose CH or whether levels overlap between patients with and without CH. (LLM, conf=0.76)

  cites [75] Krasowski, 2014, Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction, BMC Clin Pathol sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [77] Persani, 2000, Circulating thyrotropin bioactivity in sporadic central hypothyroidism, J Clin Endocrinol Metab source

In the paper

“Acute/subacute illness alters T levels acting at various levels of the hypothalamo-pituitary-gonadal axis (90,91).”

What the sources say

• ?Not checked — no full text of the sourcecites [90] Cooke, 1993, Circadian variation in serum free and non-SHBG-bound testosterone in normal men: measurements, and simulation using a mass action model, Clin Endocrinol (Oxf) source
• ?Could not verify

  The Discussion describes changes in testosterone levels by time of day and age, not by acute or subacute illness. Searches for illness and effects on the hypothalamo-pituitary-gonadal axis found no passage in our copy addressing the claimed mechanism. (LLM, conf=0.76)

  cites [91] Brambilla, 2009, The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured

In the paper

“Many patients with CH have undetectable TSH levels on presentation, and almost all CH patients adequately treated with L-T4 to maintain serum fT4 levels in the mid-to high-normal range will have undetectable TSH levels (75,80,127,129).”

What the sources say

• ?Could not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  cites [75] Krasowski, 2014, Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction, BMC Clin Pathol sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [80] Koulouri, 2011, Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine, Clin Endocrinol (Oxf) source
• ?Could not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  cites [127] Ekman, 2014, European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy, BMC Endocr Disord sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [129] Shimon, 2002, Thyrotropin suppression by thyroid hormone replacement is correlated with thyroxine level normalization in central hypothyroidism, Thyroid source

In the paper

“T replacement increases libido, sexual motivation and sexual function (134,135,138-143), mood (144), sense of well being, concentration (135,139,143,145-147), self-reported sense of energy (134,135), muscle mass and strength (132,148,149), and the recovery of anemia related to T deficiency (134).”

What the sources say

• ?Not checked — no full text of the sourcecites [134] Katznelson, 1996, Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism, J Clin Endocrinol Metab source
• ?Could not verify

  The Abstract and Discussion report increased bone mineral density in hypogonadal men, not the sexual, psychological, muscular, or anemia-related outcomes in the claim. Searches for muscle strength and the other claimed outcomes found no passage reporting those effects; muscle mass and strength appear only in the title of another study in the References. (LLM, conf=0.76)

  cites [135] Behre, 1997, Long-term effect of testosterone therapy on bone mineral density in hypogonadal men, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [138] Benito, 2005, Effect of testosterone replacement on trabecular architecture in hypogonadal men, J Bone Miner Res source
• ?Could not verify

  The citation to this paper appears in the group attached to the muscle-mass-and-strength claim. The Discussion reports improved mechanical properties of tibial trabecular bone after testosterone treatment, not changes in muscle mass or strength. Searches for those outcomes and the other listed benefits found no passage in our copy that reports them. (LLM, conf=0.78)

  cites [139] Zhang, 2008, In vivo microMRI-based finite element and morphological analyses of tibial trabecular bone in eugonadal and hypogonadal men before and after testosterone treatment, J Bone Miner Res sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [140] Kwan, 1983, The nature of androgen action on male sexuality: a combined laboratory-self-report study on hypogonadal men, J Clin Endocrinol Metab source
• Partly supported

  The Sexual Activity and Mood State section reports increased sexual interest, potency, spontaneous erections and vigor during hormone replacement in previously untreated hypogonadal men. It also reports improvements in mood measures. The paper does not establish the claimed gains in concentration, muscle mass or strength, or recovery from anemia. (LLM, conf=0.86)

  cites [141] Burris, 1992, A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men, J Androl sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [142] McNicholas, 2003, A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function, BJU Int source
• ?Not checked — no full text of the sourcecites [143] Seftel, 2004, Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning, J Androl source
• ?Not checked — no full text of the sourcecites [144] Boloña, 2007, Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials, Mayo Clin Proc source
• ?Not checked — no full text of the sourcecites [145] Zitzmann, 2013, IPASS: a study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men, J Sex Med source

In the paper

“Treatment increases BMD (132-135) and improves trabecular structure (136) and bone mechanical properties (137).”

What the sources say

• ?Not checked — no full text of the sourcecites [132] Gordon, 1999, Variations in adequate levothyroxine replacement therapy in patients with different causes of hypothyroidism, Endocr Pract source
• ?Not checked — no full text of the sourcecites [133] Mazziotti, 2014, Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism, Eur J Endocrinol source
• ?Not checked — no full text of the sourcecites [134] Katznelson, 1996, Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism, J Clin Endocrinol Metab source
• Supported

  This source is cited for the BMD portion of the sentence (132–135), not for trabecular structure or mechanical properties (136–137). The Discussion reports that long-term testosterone therapy significantly increases BMD in hypogonadal men; page numbers are not provided for the passages. (LLM, conf=0.93)

  cites [135] Behre, 1997, Long-term effect of testosterone therapy on bone mineral density in hypogonadal men, J Clin Endocrinol Metab source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [136] Snyder, 2000, Effects of testosterone replacement in hypogonadal men, J Clin Endocrinol Metab
• Supported

  The citation is attached to the BMD portion of the sentence, not the separately cited claims about trabecular structure or bone mechanical properties. The Discussion reports that BMD increased at the hip and spine during testosterone replacement in hypogonadal men. (LLM, conf=0.93)

  cites [137] Wang, 2004, Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men, J Clin Endocrinol Metab source

In the paper

“Primary ovarian failure is associated with reduced BMD and increased risk of fractures (154-156), and estrogen replacement protects against fractures (154,157,158).”

What the sources say

• ?Not checked — no full text of the sourcecites [154] Cardozo, 2004, A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder, Acta Obstet Gynecol Scand source
• ?Not checked — no full text of the sourcecites [155] Tuppurainen, 1995, Risks of perimenopausal fractures–a prospective population-based study, Acta Obstet Gynecol Scand source
• ?Not checked — no full text of the sourcecites [156] van Der Voort, 2003, Early menopause: increased fracture risk at older age, Osteoporos Int source
• Partly supported

  The Abstract and Discussion report that women with primary ovarian insufficiency had lower BMD than controls. The Modifiable risk factors section associates not taking hormone replacement with low BMD, but does not establish protection against fractures. The Discussion says prospective fracture-rate studies are needed to establish the link between estrogen deficiency and fracture risk in this population. (LLM, conf=0.88)

  cites [157] Popat, 2009, Bone mineral density in estrogen-deficient young women, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [158] Lindsay, 1980, Prevention of spinal osteoporosis in oophorectomised women, Lancet source

In the paper

“Studies, primarily in women close to or after the natural age of menopause, have shown that oral estrogen or combined estrogen/progestogen therapy are very effective in alleviating vasomotor symptoms of hypoestrogenism (hot flushes and night sweats) (151) and improving vaginal atrophy (152), urinary frequency, and dysuria (153).”

What the sources say

• ?Could not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  cites [151] Swerdloff, 2015, Serum testosterone (T) level variability in T gel-treated older hypogonadal men: treatment monitoring implications, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [152] Maclennan, 2004, Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes, Cochrane Database Syst Rev source
• ?Not checked — no full text of the sourcecites [153] Cardozo, 1998, Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee, Obstet Gynecol source

In the paper

“The hypothalamic-pituitary-thyroid axis also influences GH dynamics, with altered GH and IGF-1 secretion occurring in hypothyroidism (34).”

What the sources say

• Supported

  The “Growth hormone and the thyroid” section (p. 2) says the HPT axis influences GH secretion and action. The “Thyroid hormone effect on the GH-IGF-I axis” section (p. 2) reports reduced IGF-I in untreated primary hypothyroidism and decreased GH pulsatility and response to secretagogues in hypothyroidism. (LLM, conf=0.94)

  cites [34] Behan, 2011, The interaction between growth hormone and the thyroid axis in hypopituitary patients, Clin Endocrinol (Oxf) source

In the paper

“Increased bone mass occurs after 12 months (173), and fracture development is slowed in patients with no previous osteoporosis (159).”

What the sources say

• ?Not checked — no full text of the sourcecites [173] Maison, 2004, Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a metaanalysis of blinded, randomized, placebo-controlled trials, J Clin Endocrinol Metab source
• Partly supported

  The Unadjusted analyses (p. 4) show fewer incident vertebral fractures among participants with no vertebral fracture at baseline than among those with a prior vertebral fracture. The paper does not establish that these participants had no previous osteoporosis or that fracture development was slowed; it reports an association with fracture history, not a change in the rate of development. (LLM, conf=0.78)

  cites [159] van der Klift, 2004, Risk factors for incident vertebral fractures in men and women: the Rotterdam Study, J Bone Miner Res sourceExperimental — accuracy not yet measured

In the paper

“Oral estrogen therapy increases circulating CBG (through a hepatic first-pass effect), leading to increased total cortisol levels; this does not occur with transdermal estrogen therapy (189,190).”

What the sources say

• ?Not checked — no full text of the sourcecites [189] Giavoli, 2004, Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients, J Clin Endocrinol Metab source
• ?Could not verify

  The Glucocorticoids section (page unavailable) discusses cortisol and glucocorticoid effects on TSH, not estrogen therapy. Searches for oral and transdermal estrogen, cortisol-binding globulin, and hepatic first-pass effects found no passage addressing the claimed difference in total cortisol levels. (LLM, conf=0.76)

  cites [190] Haugen, 2009, Drugs that suppress TSH or cause central hypothyroidism, Best Pract Res Clin Endocrinol Metab sourceExperimental — accuracy not yet measured

In the paper

“In a randomized placebo-controlled study, mean GH doses of 0.58 mg/day resulted in decreased visceral fat mass and improved QOL indices (231).”

What the sources say

• Partly supported

  The Introduction (page not provided) reports that GH replacement improves body composition and quality of life in cured acromegalic patients with GH deficiency. It does not report a 0.58 mg/day dose, a decrease specifically in visceral fat, or those outcomes from a randomized placebo-controlled study. The References list such a trial, but the cited paper does not link it to the claimed dose and outcomes. (LLM, conf=0.84)

  cites [231] Ku, 2014, Clinical predictors of GH deficiency in surgically cured acromegalic patients, Eur J Endocrinol sourceExperimental — accuracy not yet measured

In the paper

“T therapy in males with central hypogonadism reduces fat mass and increases fat-free mass (132,135,140,148,149).”

What the sources say

• ?Not checked — no full text of the sourcecites [132] Gordon, 1999, Variations in adequate levothyroxine replacement therapy in patients with different causes of hypothyroidism, Endocr Pract source
• ?Could not verify

  The Patients section includes men with secondary hypogonadism, but the study measures bone mineral density, not changes in body composition. The Results and Discussion report increased bone mineral density with therapy; searches for fat mass, fat-free mass, and body composition found no passage supporting the claimed effects. (LLM, conf=0.76)

  cites [135] Behre, 1997, Long-term effect of testosterone therapy on bone mineral density in hypogonadal men, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [140] Kwan, 1983, The nature of androgen action on male sexuality: a combined laboratory-self-report study on hypogonadal men, J Clin Endocrinol Metab source
• Partly supported

  The Introduction reports improvements in body weight and waist circumference with testosterone replacement therapy, and the Results report patient-perceived improvement in muscle mass. Neither passage establishes reduced fat mass and increased fat-free mass specifically in men with central hypogonadism; the paper's mention of hypogonadotropic hypogonadism concerns secondary sexual characteristics instead. (LLM, conf=0.82)

  cites [148] Kovac, 2014, Patient satisfaction with testosterone replacement therapies: the reasons behind the choices, J Sex Med sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [149] Brodsky, 1996, Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men–a clinical research center study, J Clin Endocrinol Metab source

In the paper

“Partial or complete hypopituitarism is a prominent feature and contributes to high mortality (257,258).”

What the sources say

• ?Not checked — no full text of the sourcecites [257] Källén, 1995, Diabetes insipidus and use of desmopressin (Minirin) during pregnancy, Eur J Endocrinol source
• ?Could not verify

  The Background Characteristics section describes pituitary hormone deficiencies in pregnant patients with growth hormone deficiency, but does not identify pituitary apoplexy as their cause. A search of our copy for pituitary apoplexy and mortality found no passage addressing whether hypopituitarism is a prominent feature of apoplexy or contributes to mortality. (LLM, conf=0.76)

  cites [258] Vila, 2015, Pregnancy outcomes in women with growth hormone deficiency, Fertil Steril sourceExperimental — accuracy not yet measured

In the paper

“Some AEDs enhance hepatic CYP450 isoenzyme activity (e.g., phenytoin, carbamazepine, oxcarbazepine, and topiramade), accelerating the hepatic metabolism of hormonal preparations and decreasing serum concentrations of relevant hormones (268).”

What the sources say

• ?Could not verify

  The Patient Outcomes and Treatment sections discuss hormone deficiencies and replacement after pituitary apoplexy, but not antiepileptic drugs or drug-induced hormone metabolism. Searches for AEDs, CYP450, the named drugs, and hepatic metabolism found no passage addressing the claimed mechanism. Page numbers were not available in our copy. (LLM, conf=0.78)

  cites [268] Verrees, 2004, Pituitary tumor apoplexy: characteristics, treatment, and outcomes, Neurosurg Focus sourceExperimental — accuracy not yet measured

In the paper

“GC recommendations are relatively similar in central AI and primary AI; however, patients with central AI do not require mineralocorticoid replacement.”

What the sources say

• Partly supported

  The General Introduction (page unavailable) distinguishes primary adrenal insufficiency from secondary insufficiency, stating that the latter does not affect the renin–angiotensin–aldosterone system; this supports the mineralocorticoid distinction. The Evidence section describes glucocorticoid replacement for primary adrenal insufficiency, but our copy does not compare its recommendations with those for central adrenal insufficiency. (LLM, conf=0.82)

  cites [72] Bornstein, 2016, Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured

In the paper

“Other AEDs increase SHBG, leading to the reduced bioavailability of E2 and T (268), which may compromise the efficacy of hormonal treatment.”

What the sources say

• ?Could not verify

  The Patient Outcomes and Treatment sections discuss hormone replacement after pituitary apoplexy, not antiepileptic drugs or sex hormone–binding globulin (page numbers unavailable). Searches for AEDs, SHBG, and reduced estradiol or testosterone bioavailability found no passage addressing the cited claim. (LLM, conf=0.76)

  cites [268] Verrees, 2004, Pituitary tumor apoplexy: characteristics, treatment, and outcomes, Neurosurg Focus sourceExperimental — accuracy not yet measured

In the paper

“Differences in anterior and posterior pituitary blood supply may explain the relative sparing of ADH secretion (258).”

What the sources say

• Partly supported

  Background Characteristics (page unavailable) reports ADH deficiency in 28% of these women, less often than the other listed pituitary deficiencies. The paper does not discuss differences in anterior and posterior pituitary blood supply or propose them as an explanation for relative sparing of ADH secretion. (LLM, conf=0.83)

  cites [258] Vila, 2015, Pregnancy outcomes in women with growth hormone deficiency, Fertil Steril sourceExperimental — accuracy not yet measured

In the paper

“Dexamethasone is metabolized primarily by hepatic CYP3A4 (269), and patients may need to increase dexamethasone doses (268).”

What the sources say

• ?Could not verify

  The Treatment section discusses steroid replacement for pituitary tumor apoplexy and specifies intravenous hydrocortisone, but does not address dexamethasone dose increases. Searches for dexamethasone with enzyme-inducing antiepileptic drugs and for CYP3A4 metabolism found no passage addressing the claimed interaction. Page numbers were not available in our copy. (LLM, conf=0.77)

  cites [268] Verrees, 2004, Pituitary tumor apoplexy: characteristics, treatment, and outcomes, Neurosurg Focus sourceExperimental — accuracy not yet measured

In the paper

“Studies have reported that 44-62% of cases experience a reversal of hypogonadism, usually within 6 months after starting treatment (225,226).”

What the sources say

• ?Not checked — no full text of the sourcecites [225] Pecori Giraldi, 2007, Significant GH deficiency after long-term cure by surgery in adult patients with Cushing’s disease, Eur J Endocrinol source
• Partly supported

  Section 4.1 (Remarks) identifies reversal of hypogonadism as a goal of dopamine-agonist treatment. Section 4.1 (Evidence) reports prolactin normalization within six months in some patients with macroprolactinomas, but does not report that 44–62% experienced reversal of central hypogonadism or that reversal usually occurred within six months. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  cites [226] Melmed, 2011, Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured

In the paper

“Meta-analysis did not show an association between GH replacement and pituitary tumor recurrence (RR 0.87; 95% CI, 0.56-1.33)or the risk of secondary malignancies (RR 1.24; 95% CI, 0.65-2.33).”

In the paper

“Each review addressed a question of association and both demonstrated that the evidence (overall) warrants low certainty in the provided estimates.”

In the paper

“Factors associated with increased mortality were female gender, younger age at diagnosis, an underlying diagnosis of a craniopharyngioma or aggressive tumor, the presence of DI, and prior treatment with surgery or radiotherapy.”

In the paper

“Clinicians could observe reductions of up to 60% for FSH and 50% for LH.”

What the sources say

• ?Not checked — no full text of the sourcecites [101] Drincic, 2003, Men with acquired hypogonadotropic hypogonadism treated with testosterone may be fertile, Pituitary source

In the paper

“In 2,737 adult hypopituitary patients (122), those receiving the equivalent of ≤10 mg HC had the best QOL, and those receiving ≥25 mg HC had the poorest QOL.”

What the sources say

• ?Not checked — no full text of the sourcecites [122] Peacey, 1997, Glucocorticoid replacement therapy: are patients over treated and does it matter?, Clin Endocrinol (Oxf) source

In the paper

“The HC 10 mg a.m./5 mg p.m. regimen showed improved physical QOL, but overall QOL did not differ between regimens and remained lower than in healthy controls.”

What the sources say

• ?Not checked — no full text of the sourcecites [121] Mager, 2003, Integrated QSPR–pharmacodynamic model of genomic effects of several corticosteroids, J Pharm Sci source

In the paper

“However, a recent publication reported that increased risk of vertebral fracture in hypopituitary patients receiving higher daily doses of L-T4 correlated with higher fT4 levels (131).”

What the sources say

• ?Not checked — no full text of the sourcecites [131] Klose, 2013, Central hypothyroidism and its replacement have a significant influence on cardiovascular risk factors in adult hypopituitary patients, J Clin Endocrinol Metab source

In the paper

“A randomized controlled study of CH (80) measured fT4 levels 2 hours after dose ingestion and reported slightly elevated mean fT4 levels with adequate doses.”

What the sources say

• ?Not checked — no full text of the sourcecites [80] Koulouri, 2011, Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine, Clin Endocrinol (Oxf) source

In the paper

“Interestingly, the female sex and presence of DI in AC correlated with hospital admission in one study (29).”

What the sources say

• ?Not checked — no full text of the sourcecites [29] Hahner, 2015, High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study, J Clin Endocrinol Metab source

In the paper

“Studies have not associated HRT in women 40-49 years with increased risk of breast cancer (161), and there is no evidence that estrogen replacement in women with premature ovarian failure relates to a higher risk of breast cancer ( 162).”

What the sources say

• ?Not checked — no full text of the sourcecites [161] Mazziotti, 2010, Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency, Eur J Endocrinol source
• ?Not checked — no full text of the sourcecites [162] Stuenkel, 2015, Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab source

In the paper

“When clinicians substituted L-T3 for some of the L-T4, working memory was slightly better but at the expense of T3 levels above the reference range.”

What the sources say

• ?Not checked — no full text of the sourcecites [80] Koulouri, 2011, Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine, Clin Endocrinol (Oxf) source

In the paper

“Increasing the L-T4 dose from a mean of 1.0 to a mean of 1.6 mcg/kg/day led to mild weight loss; improvements in hypothyroid symptom scores; and decreased BMI, total and LDL cholesterol levels, and serum CK levels.”

What the sources say

• ?Not checked — no full text of the sourcecites [80] Koulouri, 2011, Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine, Clin Endocrinol (Oxf) source

In the paper

“The effects of GH replacement on BMD are more beneficial in men (172) and with patients that have severe bone loss.”

What the sources say

• ?Not checked — no full text of the sourcecites [172] Widdowson, 2008, The effect of growth hormone replacement on exercise capacity in patients with GH deficiency: a metaanalysis, J Clin Endocrinol Metab source

In the paper

“Oral and sublingual DDAVP absorption rates are <1%, while intranasal is ~6% (180).”

What the sources say

• ?Not checked — no full text of the sourcecites [180] Juul, 2011, Desmopressin duration of antidiuretic action in patients with central diabetes insipidus, Endocrine source

In the paper

“Administering GH to GHD adults causes variable changes in thyroid hormone levels-the most consistent effect being decreased fT4 levels (81,191,192).”

What the sources say

• ?Not checked — no full text of the sourcecites [81] Slawik, 2007, Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine, J Clin Endocrinol Metab source
• ?Not checked — no full text of the sourcecites [191] Shifren, 2007, A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women, Menopause source
• ?Not checked — no full text of the sourcecites [192] Qureshi, 2007, The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol, Clin Endocrinol (Oxf) source

In the paper

“All assays exhibited adequate sensitivity and acceptable intra-assay variability at <20% (Appendix A).”

In the paper

“Although, it is difficult to confirm this, since by definition many healthy subjects have fT4 levels in the lower part of the laboratory reference range, and there are no validated measures of thyroid function in hypopituitary patients.”

In the paper

“Those with GHD are less often working full time, and more often on sick leave/disability, often live alone, and often with parents (14).”

What the sources say

• ?Not checked — no full text of the sourcecites [14] Holmer, 2013, Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy, Psychoneuroendocrinology source

In the paper

“GHD is measured via insulin tolerance, glucagon, and (if available) GHRH + arginine tests.”

In the paper

“1.3 We suggest that a cortisol level <3 mcg/dl is indicative of AI, and a cortisol level >15 mcg/dl likely excludes an AI diagnosis.(2|⊕OOO)”

In the paper

“However, GH replacement may reduce excess mortality from an SMR of 2.40 (95% CI 1.46-3.34) to 1.99 (95% CI 1.21-2.76),especially in men (60).”

What the sources say

• ?Not checked — no full text of the sourcecites [60] Pappachan, 2015, Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies, J Clin Endocrinol Metab source

In the paper

“However this evidence may or may not be directly applicable to central pituitary deficiencies.”

In the paper

“These patients often have a blunted or absent nocturnal surge in TSH levels, but this is impractical for diagnostic use (33).”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Persani, 2012, Clinical review: central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges, J Clin Endocrinol Metab source

In the paper

“Accordingly, clinicians cannot use TSH levels alone to diagnose or monitor CH.”

In the paper

“As GCs suppress the HPA axis, and there are interferences in cortisol measurements, clinicians should perform biochemical testing at least 18-24 hours after the last HC dose or longer for synthetic GCs (74).”

What the sources say

• ?Not checked — no full text of the sourcecites [74] Ospina, 2016, ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis, J Clin Endocrinol Metab source

In the paper

“However, this approach may miss a significant number of patients with mild CH, as some pituitary patients with low-normal fT4 levels may have mild CH.”

In the paper

“Therefore, it can be challenging to ascribe specific features to a single hormone deficiency.”

In the paper

“TSH levels in CH may be low, normal, or slightly elevated, reflecting decreased 24-hour secretion and altered bioactivity with relatively preserved immunoactivity (75)(76)(77).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites (75)(76)(77)

In the paper

“Androgen deprivation therapy in prostate cancer is associated with an increased incidence of myocardial infarctions and cardiovascular mortality (41)(42)(43) due to increased body weight, decreased lean body mass, increased serum low-density lipoprotein (LDL) and triglycerides, and reduced insulin sensitivity (43)(44)(45)(46).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites (41)(42)(43)

In the paper

“Hypopituitary patients exhibit increased incapacitation and sick days, lower health status, and higher cost of care (12,13).”

What the sources say

• ?Not checked — no full text of the sourcecites [12] Hakkaart-van Roijen, 1998, The burden of illness of hypopituitary adults with growth hormone deficiency, Pharmacoeconomics source
• ?Not checked — no full text of the sourcecites [13] Ehrnborg, 2000, Cost of illness in adult patients with hypopituitarism, Pharmacoeconomics source

In the paper

“Past studies have attempted to categorize CH based on TSH responsiveness to exogenous TSHreleasing hormone administration (83), but this has not proven to be useful in clinical practice.”

What the sources say

• ?Not checked — no full text of the sourcecites [83] Doin, 2012, Diagnosis of subclinical central hypothyroidism in patients with hypothalamic-pituitary disease by Doppler echocardiography, Eur J Endocrinol source

In the paper

“Diagnosis in adults with a prior diagnosis of childhood-onset GHD (congenital or acquired) is relatively straightforward, as these patients had short stature.”

In the paper

“However, as clinical features of acquired AGHD are often subtle, not necessarily specific to an underlying pituitary disorder, and commonly encountered in the general population, these patients should all be re-tested as adults.”

In the paper

“One study reported a SMR of 2.09 (95% CI 0.94-4.65) in females with untreated gonadotropin deficiency and an SMR of 0.94 (95% CI 0.35-2.49) in those with treated hypogonadism (52).”

What the sources say

• ?Not checked — no full text of the sourcecites [52] Lindholm, 2006, Hypopituitarism and mortality in pituitary adenoma, Clin Endocrinol (Oxf) source

In the paper

“Weight-adjusted, 3-times-daily dosing using HC reduces GC overexposure and represents the most refined regime available, although it does not replicate the normal cortisol rhythm (113).”

What the sources say

• ?Not checked — no full text of the sourcecites [113] Mah, 2004, Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency, Clin Endocrinol (Oxf) source

In the paper

“As no reliable marker to determine exact GC needs is available, initial dose requirements are largely estimated.”

In the paper

“Systemic diseases, eating disorders, extensive exercise, and a number of medications or recreational drugs (e.g., GCs, opiates, ketoconazole, barbiturates, cocaine) affect T levels (92,93).”

What the sources say

• ?Not checked — no full text of the sourcecites [92] Spratt, 1992, Both hyper- and hypogonadotropic hypogonadism occur transiently in acute illness: bio- and immunoactive gonadotropins, J Clin Endocrinol Metab source
• ?Not checked — no full text of the sourcecites [93] Zitzmann, 2001, Testosterone levels in healthy men and the relation to behavioural and physical characteristics: facts and constructs, Eur J Endocrinol source

In the paper

“T levels demonstrate an age-related decline (96,97).”

What the sources say

• ?Not checked — no full text of the sourcecites [96] Brambilla, 2007, Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men, Clin Endocrinol (Oxf) source
• ?Not checked — no full text of the sourcecites [97] Bhasin, 2010, Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab source

In the paper

“Furthermore, one study proposed that in patients with hypogonadotropic hypogonadism the GnRH responses are variable and depend on the severity of gonadotropin deficiency, which is often reflected by the clinical phenotype (100).”

What the sources say

• ?Not checked — no full text of the sourcecites [100] Dunn, 1981, Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma, J Clin Endocrinol Metab source

In the paper

“About 2% of circulating T is free (unbound), 44% is bound to sex hormone-binding globulin (SHBG), and 54% is bound to albumin and other proteins (98).”

What the sources say

• ?Not checked — no full text of the sourcecites [98] Feldman, 2002, Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study, J Clin Endocrinol Metab source

In the paper

“The authors recommended against the routine use of dehydroepiandrosterone due to limited MAY 4, 2016 data concerning its effectiveness and safety in women with AI.”

What the sources say

• ?Not checked — no full text of the sourcecites [126] Johannsson, 2012, Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation, J Clin Endocrinol Metab source

In the paper

“The same authors also recommended against the routine prescription of T in women with hypopituitarism (126).”

What the sources say

• ?Not checked — no full text of the sourcecites [126] Johannsson, 2012, Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation, J Clin Endocrinol Metab source

In the paper

“Daily physiologic cortisol production in healthy individuals is about 5-10 mg per square meter of body surface area (107), corresponding to a replacement dose of approximately 15-20 mg/day.”

What the sources say

• ?Not checked — no full text of the sourcecites [107] Kane, 2007, Measurement of serum testosterone in women; what should we do?, Ann Clin Biochem source

In the paper

“11 β-hydroxisteroid dehydrogenase-1 converts cortisone acetate to biologically active cortisol, which might reduce circulating cortisol fluctuations (110).”

What the sources say

• ?Not checked — no full text of the sourcecites [110] Howlett, 1997, An assessment of optimal hydrocortisone replacement therapy, Clin Endocrinol (Oxf) source

In the paper

“Urine-free cortisol measurements have wide inter-and intra-variability, and thus are rarely useful MAY 4, 2016 (109,110).”

What the sources say

• ?Not checked — no full text of the sourcecites [109] Esteban, 1991, Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry, J Clin Endocrinol Metab source
• ?Not checked — no full text of the sourcecites [110] Howlett, 1997, An assessment of optimal hydrocortisone replacement therapy, Clin Endocrinol (Oxf) source

In the paper

“Normal GH secretion is characterized by a heterogeneous pulsatile pattern; therefore, measuring basal circulating GH MAY 4, 2016 levels does not provide useful diagnostic information.”

In the paper

“Unlike GH, IGF-1 levels are relatively reproducible and stable, with a circulating half-life of 24-30 hours.”

In the paper

“Published surveys of current practice for GC replacement therapy include mostly patients with primary AI, however some studies also include patients with central AI (116).”

What the sources say

• ?Not checked — no full text of the sourcecites [116] Hameed, 2013, Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing’s disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience, Pituitary source

In the paper

“Studies on this topic are limited in that they employed various T formulations with different MAY 4, 2016 regimes, were usually short duration with a small number of patients, and were not randomized placebocontrolled.”

In the paper

“GH therapy is approved for replacement in adults with rigorously proven GHD or for treating HIVrelated muscle wasting (164).”

What the sources say

• ?Not checked — no full text of the sourcecites [164] Pitkin, 2007, Management of premature menopause, Menopause Int source

In the paper

“As there are no studies on premenopausal women with central hypogonadism, for this group of female patients clinicians often refer to the published results from women with primary hypogonadism.”

In the paper

“Few studies have examined the use of L-T3 or other formulations of thyroid hormone for CH (80); there are no high-quality studies that document the superiority of these treatments over L-T4 in primary hypothyroidism, and there are potential safety concerns (reviewed in 76).”

What the sources say

• ?Not checked — no full text of the sourcecites [80] Koulouri, 2011, Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine, Clin Endocrinol (Oxf) source
• ?Not checked — no full text of the sourcecites [76] Ferretti, 1999, Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism, J Clin Endocrinol Metab source

In the paper

“As women exhibit features of relative GH resistance, they usually require higher starting and maintenance replacement GH doses, as do women receiving oral estrogens (165).”

What the sources say

• ?Not checked — no full text of the sourcecites [165] King, 2011, Hormone replacement therapy and women with premature menopause–a cancer survivorship issue, Eur J Cancer source

In the paper

“This is because thyroid hormone accelerates endogenous cortisol clearance and could unmask insufficient cortisol production and precipitate AC.”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Persani, 2012, Clinical review: central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges, J Clin Endocrinol Metab source

In the paper

“Oral estrogen treatment leads to decreased circulating IGF-1 levels in GHD women resulting in increased postprandial lipid oxidation and decreased protein synthesis, which antagonizes the metabolic actions of GH.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites (197)(198)(199)

In the paper

“This does not occur with transdermally-administered estrogen, suggesting a first-pass effect of estrogen and the inhibition of hepatic GH actions (197)(198)(199).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites (197)(198)(199)

In the paper

“Clinicians could overdiagnose GHD in the setting of CH and should treat CH prior to performing stimulation tests for GHD.”

In the paper

“These effects can decrease fT4 levels into the hypothyroid range, suggesting that untreated GHD can mask CH by artificially maintaining fT4 levels in the reference range.”

What the sources say

• ?Not checked — no full text of the sourcecites [81] Slawik, 2007, Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine, J Clin Endocrinol Metab source
• ?Not checked — no full text of the sourcecites [191] Shifren, 2007, A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women, Menopause source
• ?Not checked — no full text of the sourcecites [192] Qureshi, 2007, The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol, Clin Endocrinol (Oxf) source

In the paper

“IGF-1 levels are reduced in hypothyroidism, and GH stimulation with insulin or GH-releasing hormone may be blunted (185,195).”

What the sources say

• ?Not checked — no full text of the sourcecites [185] Stewart, 2001, Growth hormone, insulin-like growth factor-I and the cortisol-cortisone shuttle, Horm Res source
• ?Not checked — no full text of the sourcecites [195] Agha, 2007, Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients, Clin Endocrinol (Oxf) source

In the paper

“This is particularly important in elderly individuals who may have increased renal sensitivity to the drug and/or may have abnormalities in osmoregulation (179).”

What the sources say

• ?Not checked — no full text of the sourcecites [179] Behan, 2015, Abnormal plasma sodium concentrations in patients treated with desmopressin for cranial diabetes insipidus: results of a long-term retrospective study, Eur J Endocrinol source

In the paper

“As GH suppresses the conversion of cortisone to cortisol, patients receiving GC replacement may require higher doses once GH is initiated, and those with low adrenal reserve may be rendered hypoadrenal by the GH therapy (183,187).”

What the sources say

• ?Not checked — no full text of the sourcecites [183] Oiso, 2013, Clinical review: treatment of neurohypophyseal diabetes insipidus, J Clin Endocrinol Metab source
• ?Not checked — no full text of the sourcecites [187] Filipsson, 2009, GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies, Eur J Endocrinol source

In the paper

“Cortisol secretion in the first 24 hours after surgery rarely exceeds 200 mg and correlates with the duration and extent of surgery (247).”

What the sources say

• ?Not checked — no full text of the sourcecites [247] Raff, 1990, Cortisol inhibition of vasopressin and ACTH responses to arterial hypotension in conscious dogs, Am J Physiol source

In the paper

“In these patients, immediate (72 hours) postoperative GH levels, as well as the bilaterality of intrasellar tumor involvement, are significant determinants of subsequent GHD (seen in about 10% of patients) (229).”

What the sources say

• ?Not checked — no full text of the sourcecites [229] Warfield, 1984, Bromocriptine treatment of prolactin-secreting pituitary adenomas may restore pituitary function, Ann Intern Med source

In the paper

“Adults secrete 75-100 mg of cortisol per day in response to major surgery and 50 mg per day in response to minor surgery (247).”

What the sources say

• ?Not checked — no full text of the sourcecites [247] Raff, 1990, Cortisol inhibition of vasopressin and ACTH responses to arterial hypotension in conscious dogs, Am J Physiol source

In the paper

“One study suggests new normal ranges for cortisol in pregnancy (251).”

What the sources say

• ?Not checked — no full text of the sourcecites [251] Glowniak, 1997, A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency, Surgery source

In the paper

“Other causes of postsurgical abundant diuresis include steroid-induced hyperglycemia, abundant intraoperative fluid administration, and (in the case of acromegaly) an abrupt reduction of serum GH levels (241).”

What the sources say

• ?Not checked — no full text of the sourcecites [241] Ladenson, 1984, Complications of surgery in hypothyroid patients, Am J Med source

In the paper

“Short-term GC replacement increase (7-day increase in HC to 30 mg/day) (206) resulted in reduced endothelial function and improved left ventricular systolic loading.”

What the sources say

• ?Not checked — no full text of the sourcecites [206] Walker, 2007, Glucocorticoids and cardiovascular disease, Eur J Endocrinol source

In the paper

“A prospective study of 42 subjects reported that GH replacement enhanced QOL and improved both body composition and lipid profiles (232).”

What the sources say

• ?Not checked — no full text of the sourcecites [232] Tritos, 2014, Effects of long-term growth hormone replacement in adults with growth hormone deficiency following cure of acromegaly: a KIMS analysis, J Clin Endocrinol Metab source

In the paper

“High-dose perioperative GCs increase the incidence of postoperative DI, possibly mediated by an increased glomerular filtration rate (242), reduced ADH secretion, and reduced renal sensitivity to GCs (243-245).”

What the sources say

• ?Not checked — no full text of the sourcecites [242] Weinberg, 1983, Outcome of anesthesia and surgery in hypothyroid patients, Arch Intern Med source
• ?Not checked — no full text of the sourcecites [243] Devin, 2012, Hypopituitarism and central diabetes insipidus: perioperative diagnosis and management, Neurosurg Clin N Am source
• ?Not checked — no full text of the sourcecites [244] Zada, 2010, Significance of postoperative fluid diuresis in patients undergoing transsphenoidal surgery for growth hormone-secreting pituitary adenomas, J Neurosurg source
• ?Not checked — no full text of the sourcecites [245] Rajaratnam, 2003, Hydrocortisone dose and postoperative diabetes insipidus in patients undergoing transsphenoidal pituitary surgery: a prospective randomized controlled study, Br J Neurosurg source

In the paper

“Pituitary apoplexy is a life-threatening acute pituitary infarction, hemorrhage, and/or necrosis presenting as rapid onset headache, and may include vomiting, fever, meningismus, vision abnormalities, and changes in mental status (256).”

What the sources say

• ?Not checked — no full text of the sourcecites [256] Ball, 2007, Vasopressin and disorders of water balance: the physiology and pathophysiology of vasopressin, Ann Clin Biochem source

In the paper

“Hypopituitarism may be permanent or transient after pituitary apoplexy, with recovery occurring from weeks to months from the initial event.(265)”

What the sources say

• ?Not checked — no full text of the sourcecites [265] Randeva, 1999, Classical pituitary apoplexy: clinical features, management and outcome, Clin Endocrinol (Oxf) source

In the paper

“Pituitary dysfunction may be due to preexisting deficiencies (20)(21)(22) or occurs quickly from a rapid increase of intrasellar pressure (257).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites (20)(21)(22)
• ?Not checked — no full text of the sourcecites [257] Källén, 1995, Diabetes insipidus and use of desmopressin (Minirin) during pregnancy, Eur J Endocrinol source

In the paper

“In general, the DDAVP requirement is unchanged, but it sometimes might be slightly higher (253).”

What the sources say

• ?Not checked — no full text of the sourcecites [253] Kamoun, 2014, Adrenal diseases during pregnancy: pathophysiology, diagnosis and management strategies, Am J Med Sci source

In the paper

“Many fT4 assays from pregnant patients are imprecise; an alternative approach is to monitor total T4 levels, adjusting the non-pregnant reference range upward by 50% to account for TBG effects (196).”

What the sources say

• ?Not checked — no full text of the sourcecites [196] Losa, 2008, Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency, Thyroid source

In the paper

“AEDs accelerate T4 and sex hormone clearance, and patients may require compensatory increases in hormone replacement doses (274).”

What the sources say

• ?Not checked — no full text of the sourcecites [274] Burstein, 1965, Phenobarbital-induced increase in 6-β-hydroxycortisol excretion: clue to its significance in human urine, J Clin Endocrinol Metab source

In the paper

“Transsphenoidal decompression and immediately instituting high-dose IV corticosteroid replacement therapy are the standard of care (260-262).”

What the sources say

• ?Not checked — no full text of the sourcecites [260] Arafah, 1990, Improvement of pituitary function after surgical decompression for pituitary tumor apoplexy, J Clin Endocrinol Metab source
• ?Not checked — no full text of the sourcecites [261] Veldhuis, 1980, Endocrine function after spontaneous infarction of the human pituitary: report, review, and reappraisal, Endocr Rev source
• ?Not checked — no full text of the sourcecites [262] Capatina, 2015, Management of endocrine disease: pituitary tumour apoplexy, Eur J Endocrinol source

In the paper

“However, a recent report found that oxcarbazepine increases cortisol elimination in normal MAY 4, 2016 subjects (272), suggesting that attention should also be paid to symptoms of underdosing in patients on HC.”

What the sources say

• ?Not checked — no full text of the sourcecites [272] Gentile, 1996, Dexamethasone metabolism by human liver in vitro. Metabolite identification and inhibition of 6-hydroxylation, J Pharmacol Exp Ther source

In the paper

“Lean body mass cardiac stroke volume and left ventricular mass are increased (170).”

What the sources say

• ?Not checked — no full text of the sourcecites [170] Hoffman, 2004, Growth hormone (GH) replacement therapy in adult-onset gh deficiency: effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial, J Clin Endocrinol Metab source

In the paper

“Pituitary adenomas, as well as the associated surgical and radiation treatments, can cause hypopituitarism.”

What the sources say

• ?Not checked — no full text of the sourcecites [66] Fleseriu, 2010, Normal hypothalamic-pituitary-adrenal axis by high-dose cosyntropin testing in patients with abnormal response to low-dose cosyntropin stimulation: a retrospective review, Endocr Pract source