Hypopituitarism medical therapy: Difference between revisions

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==Overview==
==Overview==
The mainstay of treatment is [[hormone replacement therapy]] and treating the underlying cause. [[Adrenocorticotropic hormone|ACTH]] deficiency is treated with [[glucocorticoids]]. [[Gonadotropin deficiency]] is treated with [[testosterone]] in men and [[estrogen]] with or without [[progesterone]] in women. [[Hypothyroidism]] is treated with [[levothyroxine]]. Growth hormone is usually replaced in children and replaced in adults only if symptomatic and after replacement of all other pituitary hormones.
The mainstay of treatment is [[hormone replacement therapy]] and treating the underlying cause. [[Adrenocorticotropic hormone|ACTH]] deficiency is treated with [[glucocorticoids]]. [[Gonadotropin deficiency]] is treated with [[testosterone]] in men and [[estrogen]] with or without [[progesterone]] in women. [[Hypothyroidism]] is treated with [[levothyroxine]]. Growth hormone is usually replaced in children and replaced in adults only if symptomatic and after replacement of all other [[pituitary]] hormones.


==Medical Therapy==
==Medical Therapy==
Line 13: Line 13:


==== Acute setting ====
==== Acute setting ====
* Preferred regimen: [[Hydrocortisone]] 100 mg IV bolus, then 300 mg/day IV divided q8hr '''or''' continuous infusion for 48 hours
* Preferred regimen: [[Hydrocortisone]] 100 mg IV bolus, then 300 mg/day IV divided q8hr '''or''' continuous [[infusion]] for 48 hours
** Once patient is stable: 50 mg PO q8hr for 6 doses, later on tapered to 30-50 mg/day PO in divided doses
** Once patient is stable: 50 mg PO q8hr for 6 doses, later on tapered to 30-50 mg/day PO in divided doses
'''Chronic setting'''   
'''Chronic setting'''   
Line 19: Line 19:
'''NOTE'''  
'''NOTE'''  
*Dosage is increased in patients with severe deficiency, increased body weight and in times of [[surgery]], [[illness]], [[Procedure|procedures]], and other [[Stress|stresses]].
*Dosage is increased in patients with severe deficiency, increased body weight and in times of [[surgery]], [[illness]], [[Procedure|procedures]], and other [[Stress|stresses]].
*Unfortunately, there is no established test to assess adequate [[Hormone replacement therapy|hormonal replacement]]. Plasma [[Adrenocorticotropic hormone|ACTH]] measurement and [[serum]]/[[Saliva|salivary]]/[[urinary]] [[Cortisol|cortiso]]<nowiki/>l values are all unreliable. So assessment of adequate hormonal replacement is based on [[clinical]] basis with [[Cushingoid appearance|Cushingoid features]] showing excessive replacement while [[symptoms]] of [[adrenal insufficiency]] suggesting insufficient hormonal replacement.
*There is no established test to assess adequate [[Hormone replacement therapy|hormonal replacement]]. Plasma [[Adrenocorticotropic hormone|ACTH]] measurement and [[serum]]/[[Saliva|salivary]]/[[urinary]] [[Cortisol|cortiso]]<nowiki/>l values are all unreliable. So assessment of adequate hormonal replacement is based on [[clinical]] basis with [[Cushingoid appearance|cushingoid features]] showing excessive replacement while [[symptoms]] of [[adrenal insufficiency]] suggesting insufficient hormonal replacement.
*[[Glucocorticoid]] replacement can cause [[polyuria]] due to unmasking of underlying [[central diabetes insipidus]]. [[DDAVP]] is the treatment of choice for patients with [[Diabetes insipidus|DI]].<ref name="pmid18797595">{{cite journal |vauthors=Soares DV, Conceição FL, Vaisman M |title=[Clinical, laboratory and therapeutics aspects of Sheehan's syndrome] |language=Portuguese |journal=Arq Bras Endocrinol Metabol |volume=52 |issue=5 |pages=872–8 |year=2008 |pmid=18797595 |doi= |url=}}</ref>
*[[Glucocorticoid]] replacement can cause [[polyuria]] due to unmasking of underlying [[central diabetes insipidus]]. [[DDAVP]] is the treatment of choice for patients with [[Diabetes insipidus|DI]].<ref name="pmid18797595">{{cite journal |vauthors=Soares DV, Conceição FL, Vaisman M |title=[Clinical, laboratory and therapeutics aspects of Sheehan's syndrome] |language=Portuguese |journal=Arq Bras Endocrinol Metabol |volume=52 |issue=5 |pages=872–8 |year=2008 |pmid=18797595 |doi= |url=}}</ref>
*[[Mineralocorticoids]] are rarely required as [[aldosterone]] secretion is primarily regulated by [[angiotensin II]] and [[potassium]] not by [[Adrenocorticotropic hormone|ACTH]].
*[[Mineralocorticoids]] are rarely required as [[aldosterone]] secretion is primarily regulated by [[angiotensin II]] and [[potassium]] not by [[Adrenocorticotropic hormone|ACTH]].

Revision as of 15:25, 13 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

The mainstay of treatment is hormone replacement therapy and treating the underlying cause. ACTH deficiency is treated with glucocorticoids. Gonadotropin deficiency is treated with testosterone in men and estrogen with or without progesterone in women. Hypothyroidism is treated with levothyroxine. Growth hormone is usually replaced in children and replaced in adults only if symptomatic and after replacement of all other pituitary hormones.

Medical Therapy

ACTH deficiency

[15][16][17][7][18][19]

Acute setting

  • Preferred regimen: Hydrocortisone 100 mg IV bolus, then 300 mg/day IV divided q8hr or continuous infusion for 48 hours
    • Once patient is stable: 50 mg PO q8hr for 6 doses, later on tapered to 30-50 mg/day PO in divided doses

Chronic setting

NOTE

TSH deficiency:[21]

Mild hypothyroidism

Severe hypothyroidism

  • Levothyroxine 12.5-25 mcg PO qDay and later on dose can be adjusted by 25 mcg/day q2-4 Week PRN

NOTE

=== Gonadotropin deficiency: ===[22][23][24][25][26][27][28]

Men:

  • Testosterone esters (for example, Sustanon) 250 mg IM every 2–3 weeks
  • Transdermal testosterone
    • Patch (for example, Andropatch) 2.5–7.5 mg/24 hours
    • Gel (for example, Testogel) 5–10 g gel/24 hours
  • Testosterone implant 600–800 mg every 4–6 months
  • Buccal testosterone (for example, Striant SR) 1 buccal tablet (30 mg) applied to the gum every 12 hours
  • Oral testosterone (for example, Restandol) 40–120 mg daily

Women:

  • Conjugated equine oestrogens 0.625–1.25 mg daily orally

or

  • Estradiol valerate 1–2 mg daily orally
  • Transdermal estradiol (patch) 25–100 μg/24 hours
  • Oestrogen plus progesterone (cyclical/continuous): Dose depends on preparation—orally or transdermal

NOTE:

Androgen replacement:

Growth hormone replacement: [30][31][32][33][34][35]

  • Growth hormone 0.27–0.7 mg subcutaneously in the evening
  • GH is replaced on case to case basis starting with a low dose (0.1-0.3 mg/day) and titrated upwards by 0.1 mg/d/month with repeated measurement of hormone levels every month, initially for the first 6 months followed by yearly measurements; replaced once all other hormones have been replaced.[36]

ADH deficiency:

  • Desmopressin 300–600 μg daily in 2–3 divided doses orally or 10–40 μg daily in 2–3 divided doses intranasally

Prolactin deficiency:

  • A study was done on 5 women with prolactin deficiency caused by Sheehan's syndrome or other causes that showed increased milk production upon subcutaneous administration of r-hPRL (recombinant human prolactin) every 12 hours for 28 days.[37]

References

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  2. Laway BA, Bhat JR, Mir SA, Khan RS, Lone MI, Zargar AH (2010). "Sheehan's syndrome with pancytopenia--complete recovery after hormone replacement (case series with review)". Ann. Hematol. 89 (3): 305–8. doi:10.1007/s00277-009-0804-9. PMID 19697029.
  3. Tanriverdi F, Unluhizarci K, Kula M, Guven M, Bayram F, Kelestimur F (2005). "Effects of 18-month of growth hormone (GH) replacement therapy in patients with Sheehan's syndrome". Growth Horm. IGF Res. 15 (3): 231–7. doi:10.1016/j.ghir.2005.03.005. PMID 15921942.
  4. Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM (1997). "Increased cerebrovascular mortality in patients with hypopituitarism". Clin. Endocrinol. (Oxf). 46 (1): 75–81. PMID 9059561.
  5. Arafah BM (2002). "Medical management of hypopituitarism in patients with pituitary adenomas". Pituitary. 5 (2): 109–17. PMID 12675508.
  6. Grossman AB (2010). "Clinical Review#: The diagnosis and management of central hypoadrenalism". J. Clin. Endocrinol. Metab. 95 (11): 4855–63. doi:10.1210/jc.2010-0982. PMID 20719838.
  7. 7.0 7.1 Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL (1991). "Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry". J. Clin. Endocrinol. Metab. 72 (1): 39–45. doi:10.1210/jcem-72-1-39. PMID 1986026.
  8. Arlt W, Rosenthal C, Hahner S, Allolio B (2006). "Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements". Clin. Endocrinol. (Oxf). 64 (4): 384–9. doi:10.1111/j.1365-2265.2006.02473.x. PMID 16584509.
  9. Thomson AH, Devers MC, Wallace AM, Grant D, Campbell K, Freel M, Connell JM (2007). "Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency". Clin. Endocrinol. (Oxf). 66 (6): 789–96. doi:10.1111/j.1365-2265.2007.02812.x. PMID 17437510.
  10. Martin MM (1969). "Coexisting anterior pituitary and neurohypophyseal insufficiency. A syndrome with diagnostic implication". Arch. Intern. Med. 123 (4): 409–16. PMID 4182323.
  11. Shibata H, Ogishima T, Mitani F, Suzuki H, Murakami M, Saruta T, Ishimura Y (1991). "Regulation of aldosterone synthase cytochrome P-450 in rat adrenals by angiotensin II and potassium". Endocrinology. 128 (5): 2534–9. doi:10.1210/endo-128-5-2534. PMID 2019265.
  12. White PC (1994). "Disorders of aldosterone biosynthesis and action". N. Engl. J. Med. 331 (4): 250–8. doi:10.1056/NEJM199407283310408. PMID 8015573.
  13. Miller KK, Sesmilo G, Schiller A, Schoenfeld D, Burton S, Klibanski A (2001). "Androgen deficiency in women with hypopituitarism". J. Clin. Endocrinol. Metab. 86 (2): 561–7. doi:10.1210/jcem.86.2.7246. PMID 11158009.
  14. Miller KK, Biller BM, Beauregard C, Lipman JG, Jones J, Schoenfeld D, Sherman JC, Swearingen B, Loeffler J, Klibanski A (2006). "Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study". J. Clin. Endocrinol. Metab. 91 (5): 1683–90. doi:10.1210/jc.2005-2596. PMID 16478814.
  15. Peacey SR, Guo CY, Robinson AM, Price A, Giles MA, Eastell R, Weetman AP (1997). "Glucocorticoid replacement therapy: are patients over treated and does it matter?". Clin. Endocrinol. (Oxf). 46 (3): 255–61. PMID 9156031.
  16. Arlt W, Allolio B (2003). "Adrenal insufficiency". Lancet. 361 (9372): 1881–93. doi:10.1016/S0140-6736(03)13492-7. PMID 12788587.
  17. Howlett TA (1997). "An assessment of optimal hydrocortisone replacement therapy". Clin. Endocrinol. (Oxf). 46 (3): 263–8. PMID 9156032.
  18. Besser GM, Jeffcoate WJ (1976). "Endocrine and metabolic diseases. Adrenal diseases". Br Med J. 1 (6007): 448–51. PMC 1638946. PMID 3256.
  19. Peacey SR, Pope RM, Naik KS, Hardern RD, Page MD, Belchetz PE (1993). "Corticosteroid therapy and intercurrent illness: the need for continuing patient education". Postgrad Med J. 69 (810): 282–4. PMC 2399661. PMID 8321791.
  20. Soares DV, Conceição FL, Vaisman M (2008). "[Clinical, laboratory and therapeutics aspects of Sheehan's syndrome]". Arq Bras Endocrinol Metabol (in Portuguese). 52 (5): 872–8. PMID 18797595.
  21. Lamberts SW, de Herder WW, van der Lely AJ (1998). "Pituitary insufficiency". Lancet. 352 (9122): 127–34. PMID 9672293.
  22. Matsumoto AM (1994). "Hormonal therapy of male hypogonadism". Endocrinol. Metab. Clin. North Am. 23 (4): 857–75. PMID 7705324.</ref<ref name="pmid9253305">Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E (1997). "Long-term effect of testosterone therapy on bone mineral density in hypogonadal men". J. Clin. Endocrinol. Metab. 82 (8): 2386–90. doi:10.1210/jcem.82.8.4163. PMID 9253305.
  23. Torgerson DJ, Bell-Syer SE (2001). "Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials". JAMA. 285 (22): 2891–7. PMID 11401611.
  24. Armitage M, Nooney J, Evans S (2003). "Recent concerns surrounding HRT". Clin. Endocrinol. (Oxf). 59 (2): 145–55. PMID 12864790.
  25. Braunstein GD (2002). "Androgen insufficiency in women: summary of critical issues". Fertil. Steril. 77 Suppl 4: S94–9. PMID 12007911.
  26. Büchter D, Behre HM, Kliesch S, Nieschlag E (1998). "Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases". Eur. J. Endocrinol. 139 (3): 298–303. PMID 9758439.
  27. Shoham Z, Balen A, Patel A, Jacobs HS (1991). "Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients". Fertil. Steril. 56 (6): 1048–53. PMID 1743320.
  28. Morris DV, Abdulwahid NA, Armar A, Jacobs HS (1987). "The response of patients with organic hypothalamic-pituitary disease to pulsatile gonadotropin-releasing hormone therapy". Fertil. Steril. 47 (1): 54–9. PMID 3539644.
  29. Matsuzaki S, Endo M, Ueda Y, Mimura K, Kakigano A, Egawa-Takata T, Kumasawa K, Yoshino K, Kimura T (2017). "A case of acute Sheehan's syndrome and literature review: a rare but life-threatening complication of postpartum hemorrhage". BMC Pregnancy Childbirth. 17 (1): 188. doi:10.1186/s12884-017-1380-y. PMC 5471854. PMID 28615049.
  30. "Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency". J. Clin. Endocrinol. Metab. 83 (2): 379–81. 1998. doi:10.1210/jcem.83.2.4611. PMID 9467545.
  31. de Boer H, Blok GJ, Van der Veen EA (1995). "Clinical aspects of growth hormone deficiency in adults". Endocr. Rev. 16 (1): 63–86. doi:10.1210/edrv-16-1-63. PMID 7758433.
  32. Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, Laron Z, Sizonenko P, Sönksen PH, Tanaka T, Thorne M (1998). "Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee". J. Clin. Endocrinol. Metab. 83 (2): 382–95. doi:10.1210/jcem.83.2.4594. PMID 9467546.
  33. Beshyah SA, Johnston DG (1999). "Cardiovascular disease and risk factors in adults with hypopituitarism". Clin. Endocrinol. (Oxf). 50 (1): 1–15. PMID 10341850.
  34. Vance ML, Mauras N (1999). "Growth hormone therapy in adults and children". N. Engl. J. Med. 341 (16): 1206–16. doi:10.1056/NEJM199910143411607. PMID 10519899.
  35. "Critical evaluation of the safety of recombinant human growth hormone administration: statement from the Growth Hormone Research Society". J. Clin. Endocrinol. Metab. 86 (5): 1868–70. 2001. doi:10.1210/jcem.86.5.7471. PMID 11344173.
  36. Tessnow AH, Wilson JD (2010). "The changing face of Sheehan's syndrome". Am. J. Med. Sci. 340 (5): 402–6. doi:10.1097/MAJ.0b013e3181f8c6df. PMID 20944496.
  37. Powe CE, Allen M, Puopolo KM, Merewood A, Worden S, Johnson LC, Fleischman A, Welt CK (2010). "Recombinant human prolactin for the treatment of lactation insufficiency". Clin. Endocrinol. (Oxf). 73 (5): 645–53. doi:10.1111/j.1365-2265.2010.03850.x. PMID 20718766.

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References

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