Hypopituitarism medical therapy
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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 for hypopituitarism is hormone replacement therapy and treating the underlying cause. Adrenocorticotrophic 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 (GH) is usually replaced in children and replaced in adults only if symptomatic and after replacement of all other pituitary hormones.
Medical Therapy
- Treatment involves appropriate hormone replacement therapy, which must be taken for the rest of your life that results in significant improvement and reversal of not only the physical symptoms, but also the psychological symptoms.[1][2][3][4][5][6][7][8][9][10][11][12][13][14]
- Management usually involves orally-administered target organ hormone replacement except for growth hormone (GH) and antidiuretic hormone (ADH)
1.ACTH deficiency
1.1.Acute setting
- Preferred regimen: Hydrocortisone 100 mg IV bolus, then 300 mg/day IV divided q8hr or continuous infusion for 48 hours
1.2.Chronic setting
- Preferred regimen: Hydrocortisone 15-25 mg/day PO divided q8-12hr (20 mg on awakening and 10 mg in the early evening)
- Alternative regimen: Prednisone (5 mg on awakening and 2.5 mg in the early evening)
Note
- Dosage is increased in patients with severe deficiency, increased body weight, and in times of surgery, illness, procedures, and other stresses.
- There is no established test to assess adequate hormonal replacement. Plasma ACTH measurement and serum/salivary/urinary cortisol values are all unreliable. So assessment of adequate hormonal replacement is based on clinical basis with cushingoid features showing excessive replacement while symptoms of adrenal insufficiency suggesting an 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).[20]
- Mineralocorticoids are rarely required, as aldosterone secretion is primarily regulated by angiotensin II and potassium, not by ACTH.
2. TSH deficiency
2.1. Mild hypothyroidism
- Preferred regimen: Levothyroxine 1.7 mcg/kg daily or 100-125 mcg PO daily.[21]
2.2. Severe hypothyroidism
- Preferred regimen: Levothyroxine 12.5-25 mcg PO daily and later can be adjusted by 25 mcg/day q2-4 Week PRN.
Note
- In patients with combined hypothyroidism and hypocortisolism, glucocorticoids (physiologic doses and increased doses in stress) are replaced before thyroid hormone replacement, because treating the hypothyroidism alone by levothyroxine can worsen the severity of cortisol deficiency by increasing the clearance of cortisol. So, it is important to assess adrenal function, including corticotropin (ACTH) reserve, before administering T4 (levothyroxine).
- American Thyroid Association (ATA) recommends dose adjustment to keep serum free T4 concentration in upper half of reference range.
3. Gonadotropin deficiency
- Gonadotropin deficiency may be confirmed by measuring serum estradiol, testosterone, and FSH/LH levels.[22][23][24][25][26][27][28]
3.1. Men
- Preferred regimen (1): Testosterone esters (for example, Sustanon) 250 mg IM every 2–3 weeks
- Alternative regimen (1): Transdermal testosterone
- Patch (for example, Andropatch) 2.5–7.5 mg/24 hours
- Gel (for example, Testogel) 5–10 g gel/24 hours
- Alternative regimen (2): Testosterone implant 600–800 mg every 4–6 months
- Alternative regimen (3): Buccal testosterone (for example, Striant SR) 1 buccal tablet (30 mg) applied to the gum q12h
- Alternative regimen (4): Oral testosterone (for example, Restandol) 40–120 mg daily
Note
- Intramuscular route administration may result in a transient increase in serum testosterone concentrations leading to low HDL-cholesterol levels.
- Transdermal route administration may result in achieving normal physiologic levels but it is being tested.[29][30]
3.2. Women
- Preferred regimen (1): Conjugated equine estrogens 0.625–1.25 mg PO daily
- Alternative regimen (1): Estradiol valerate 1–2 mg PO daily
- Alternative regimen (2): Estradiol (patch) 25–100 μg transdermal daily
- Alternative regimen (3): Estrogen plus progesterone (cyclical/continuous): Dose depends on preparation—PO or transdermal
Note
- If fertility required
- Such women are offered ovulation induction. Pregnancy can be made possible by giving exogenous gonadotropins or pulsatile GnRH.
- Women with GnRH deficiency can be offered either pulsatile GnRH or gonadotropin therapy.
- Women with gonadotropin deficiency are given gonadotropins only.
- If fertility not required
- Such women are treated with estrogen-progestin replacement therapy by using the traditional regimen of estradiol on days 1 through 25 of each month and progesterone on days 16 through 25 of each month.
- Another regimen includes continuous transdermal estradiol throughout the month, with progestin added days 1 to 10 of the calendar month.
- For further information regarding the indications, contraindications and adverse effects of gonadotropin replacement therapy click here.
3.3. Androgen replacement
4. Growth hormone replacement
- Preferred regimen (1): Growth hormone 0.27–0.7 mg SC 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.[32]
- Growth hormone is usually replaced in children and replaced in adults only if symptomatic and after all other hormones have been replaced.[33][34][35][36][37][38]
- Growth hormone replacement is found to be associated with reduced adipose tissue, increased muscle mass, strength, bone density and improved exercise tolerance[39][40][41][42][43]
- For more information on GH replacement and complications associated with over-replacement, click here.
- Complications of growth hormone replacement therapy:[44]
- Pseudotumor cerebri
- Benign intracranial hypertension.
- Slipped capital femoral epiphyses.
- Diabetes mellitus due to insulin resistance.
5. ADH deficiency
- Preferred regimen (1): Desmopressin 300–600 μg PO daily in 2–3 divided doses OR 10–40 μg intranasally daily in 2–3 divided doses
6. Prolactin deficiency
- There is no synthetic commercial preparation available to replace prolactin.
- 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.[45]
References
- ↑ Parikh R, Buch V, Makwana M, Buch HN (2016). "The price of a 15-year delay in diagnosis of Sheehan's syndrome". Proc (Bayl Univ Med Cent). 29 (2): 212–3. PMC 4790577. PMID 27034575.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Arafah BM (2002). "Medical management of hypopituitarism in patients with pituitary adenomas". Pituitary. 5 (2): 109–17. PMID 12675508.
- ↑ 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.
- ↑ 7.0 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.
- ↑ 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.
- ↑ 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.
- ↑ Martin MM (1969). "Coexisting anterior pituitary and neurohypophyseal insufficiency. A syndrome with diagnostic implication". Arch. Intern. Med. 123 (4): 409–16. PMID 4182323.
- ↑ 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.
- ↑ White PC (1994). "Disorders of aldosterone biosynthesis and action". N. Engl. J. Med. 331 (4): 250–8. doi:10.1056/NEJM199407283310408. PMID 8015573.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Arlt W, Allolio B (2003). "Adrenal insufficiency". Lancet. 361 (9372): 1881–93. doi:10.1016/S0140-6736(03)13492-7. PMID 12788587.
- ↑ Howlett TA (1997). "An assessment of optimal hydrocortisone replacement therapy". Clin. Endocrinol. (Oxf). 46 (3): 263–8. PMID 9156032.
- ↑ Besser GM, Jeffcoate WJ (1976). "Endocrine and metabolic diseases. Adrenal diseases". Br Med J. 1 (6007): 448–51. PMC 1638946. PMID 3256.
- ↑ 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.
- ↑ 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.
- ↑ Lamberts SW, de Herder WW, van der Lely AJ (1998). "Pituitary insufficiency". Lancet. 352 (9122): 127–34. PMID 9672293.
- ↑ 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.
- ↑ 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.
- ↑ Armitage M, Nooney J, Evans S (2003). "Recent concerns surrounding HRT". Clin. Endocrinol. (Oxf). 59 (2): 145–55. PMID 12864790.
- ↑ Braunstein GD (2002). "Androgen insufficiency in women: summary of critical issues". Fertil. Steril. 77 Suppl 4: S94–9. PMID 12007911.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Findlay JC, Place VA, Snyder PJ (1987). "Transdermal delivery of testosterone". J. Clin. Endocrinol. Metab. 64 (2): 266–8. doi:10.1210/jcem-64-2-266. PMID 3793849.
- ↑ Carey PO, Howards SS, Vance ML (1988). "Transdermal testosterone treatment of hypogonadal men". J. Urol. 140 (1): 76–9. PMID 3379703.
- ↑ 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.
- ↑ 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.
- ↑ "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.
- ↑ 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.
- ↑ 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.
- ↑ Beshyah SA, Johnston DG (1999). "Cardiovascular disease and risk factors in adults with hypopituitarism". Clin. Endocrinol. (Oxf). 50 (1): 1–15. PMID 10341850.
- ↑ 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.
- ↑ "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.
- ↑ Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Ingemann-Hansen T, Skakkebaek NE, Christiansen JS (1989). "Beneficial effects of growth hormone treatment in GH-deficient adults". Lancet. 1 (8649): 1221–5. PMID 2566779.
- ↑ Salomon F, Cuneo RC, Hesp R, Sönksen PH (1989). "The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency". N. Engl. J. Med. 321 (26): 1797–803. doi:10.1056/NEJM198912283212605. PMID 2687691.
- ↑ Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH (1991). "Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength". J. Appl. Physiol. 70 (2): 688–94. PMID 2022560.
- ↑ Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH (1991). "Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance". J. Appl. Physiol. 70 (2): 695–700. PMID 2022561.
- ↑ Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Møller J, Müller J, Skakkebaek NE, Christiansen JS (1991). "Long-term growth hormone treatment in growth hormone deficient adults". Acta Endocrinol. 125 (5): 449–53. PMID 1759534.
- ↑ Bowlby DA, Rapaport R (2004). "Safety and efficacy of growth hormone therapy in childhood". Pediatr Endocrinol Rev. 2 Suppl 1: 68–77. PMID 16456485.
- ↑ 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.