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Home , Hydrocortisone, Hypopituitarism, Hypothyroidism

TREATMENT OF

Peter J Snyder, MD DISCLOSURE

Research support: AbbVie Inc TREATMENT OF HYPOPITUITARISM

 The treatment of hypopituitarism is sum of the treatments of each of the individual hormonal deficiencies detected in a patient with hypothalamic or • • Hypoadrenalism • • Hyposomatotropism  The treatments are similar in many ways to the treatments for primary deficiencies of the respective target glands, but different in other ways TREATMENT OF SECONDARY HYPOADRENALISM

 Treat with • 15-25 mg/day (similar to daily production rates) for most patients • Giving 2/3 of the daily dose on arising and 1/3 at noon makes sense physiologically, many patients cannot remember the second dose, and most patients feel well taking the entire dose on arising • No need for replacement • Sick day rules • Increase dose during to compensate for increase in CBG in pregnancy • Hydrocortisone treatment may unmask previously subclinical insipidus  Monitoring • No test exists that assesses objectively the adequacy of the replacement dose of hydrocortisone • Cannot use ACTH to monitor adequacy of hydrocortisone replacement TREATMENT OF SECONDARY HYPOTHYROIDISM

 Test adrenal function and treat secondary hypoadrenalism before or simultaneously as treating secondary hypothyroidism  Treat with  Monitor • Not TSH • Serum T4; aim to keep the serum T4 just above mid-normal based on the rationale that T3 is not being replaced  Increase dose of levothyroxine during pregnancy to compensate for the increase in TBG during pregnancy TREATMENT OF SECONDARY HYPOGONADISM - WOMEN

• Transdermal administration of estradiol preferred to oral administration – Estradiol patch or gel on days 1-25 of each month – Delivers estradiol continuously into the systemic circulation, as does ovarian secretion of estradiol (unlike an OCP that results in first pass in and increased risk of DVT) – Monitor by measuring serum estradiol  • Micronized progesterone or medroxyprogesterone acetate days 16-25 of each month  Fertility • Refer to a gynecologist specializing in fertility for ovulation induction • Good chance of fertility ESTRADIOL REPLACEMENT IN HYPOPITUITARISM

Vivelle DOT patch Estrogel TREATMENT OF SECONDARY HYPOGONADISM - MEN

 Replacement of • Any transdermal gel or intramuscular testosterone ester • Monitor efficacy by measuring serum testosterone • Monitor safety by hematocrit, DRE, PSA • Recent FDA concern about abuse of testosterone applies to idiopathic low testosterone with age, not “classical hypogonadism”  If Fertility is a Goal – • Replace LH with hCG – May be sufficient if the hypogonadism occurred after puberty – Starting dose 2000 units Monday, Wednesday, Friday – Monitor by serum testosterone and adjust dose accordingly • Replace FSH with hMG – Probably necessary if the hypogonadism occurred before puberty – Monitor by serum inhibin b and by sperm density • Refer wife to a gynecologist specializing in fertility… REPLACEMENT OF TESTOSTERONE

(Adapted from J Clin Endocrinol Metab (Adapted from J Clin Endocrinol Metab 2000; 1980; 51: 1535) 85:4500) INDUCTION OF FERTILITY IN MEN

New Engl J Med 1985; 313: 651 TREATMENT OF GROWTH DEFICIENCY

 Several preparations are approved for treating adults with growth hormone deficiency • Administer by daily subcutaneous injection (Once a week preparations are in late-phase clinical trials) • Start with a low dose and increase gradually until the serum IGF-1 reaches mid-normal for age and gender to avoid side effects  Benefits • Confirmed – Body composition: decreased fat mass; ? Increased lean mass • Demonstrated in some studies but not in others – Bone mineral density – Sense of well-being – Cardiovascular risk markers EFFECT OF GH REPLACEMENT ON BODY FAT

43 women with confirmed growth hormone deficiency due to pituitary disease were randomized to receive growth hormone or placebo for six months

(J Clin Endocrinol Metab 2008; 93:4413) EFFECT OF GH REPLACEMENT ON BMD

Patients with panhypopituitarism (40 men, 27 women) were randomized to receive growth hormone or placebo double blindly for two years. Bone mineral density of the spine was measured by DXA

(J Bone Mineral Res 2007; 22: 762) TREATMENT OF HYPOPITUITARISM – SUMMARY

 Treatment is similar to the treatment of target gland deficiencies in many ways  Treatment is different in other ways

• All target glands: The trophic hormone (eg TSH, ACTH) cannot be used to monitor treatment

• Hypoadrenalism: Hydrocortisone replacement can unmask subclinical

• Hypogonadism: Fertility can be restored in both men and women