eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Panhypopituitarism: Treatment & Medication
Updated: Oct 21, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Adrenocorticotropic hormone (ACTH) deficiency
- Cortisol deficiency requires prompt recognition and treatment. This is particularly true for the child who may be facing surgery or experiencing other significant stresses related to the cause of hypopituitarism.
- Oral replacement is usually with hydrocortisone, usually administered twice daily but can be administered 3 times daily. Prednisone may be considered advantageous because of twice-daily dosing (at about 20-25% of the dose for hydrocortisone). However, growth suppression is a more common problem with prednisone, which should generally be avoided.31
- Thyroid-stimulating hormone (TSH) deficiency
- The dose of L-thyroxine replacement is age dependent. Monitor free T4 levels and adjust the dose of T4 to maintain reference range levels.
- Evaluate and treat cortisol deficiency before starting T4 replacement to avoid precipitating an adrenal crisis.
- Gonadotropin deficiency: Begin sex steroid replacement at puberty.
- Growth hormone (GH) deficiency: Administer GH replacement in doses of 0.18-0.3 mg/kg/wk subcutaneously divided in 6-7 doses. Higher doses up to 0.7 mg/kg/wk may be beneficial in puberty.
Surgical Care
- Use surgical treatment for operable pituitary and hypothalamic tumors. If the patient has panhypopituitarism prior to surgery, pituitary function is unlikely to recover.
Consultations
- In all incidents of suspected pituitary dysfunction, a pediatric endocrinologist should be involved in the evaluation and treatment of the child.
- Determine additional consultations based on the cause of the hypopituitarism.
Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Hormones
These medications are used for replacement of deficient hormones.
Hydrocortisone (Hydrocortone, Hydrocort, Cortef, Solu-Cortef)
This drug provides cortisol replacement in patients with ACTH deficiency. Possesses both mineralocorticoid activity and glucocorticoid effects.
Adult
Pediatric
Physiologic replacement: 10-15 mg/m2/d PO divided bid/tid
Stress coverage:
Minor stress (eg, febrile illness, minor surgery): Triple PO replacement dose if able to continue PO treatment
Major stress (eg, major accident, major surgery): Administer IV or IM up to 10 times replacement dose
CYP450 2D6 and 3A3/4 substrate; corticosteroid clearance may increase with phenytoin, barbiturates, or rifampin treatment or decrease with estrogens; cholestyramine may decrease AUC; corticosteroids may increase digitalis toxicity secondary to hypokalemia; coadministration with potassium-depleting agents (eg, diuretics) may increase risk of hypokalemia; corticosteroids may decrease growth-promoting effect of GH
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
If patient is unable to take PO medication during times of stress, increased doses of hydrocortisone must be administered IV or IM; continuous IV infusion is preferable with high dose; IV bolus therapy plasma levels become suboptimal after approximately 2.5 h; if bolus therapy is used, frequency should be at least every 4 h; caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis
Levothyroxine (Levothroid, Levoxyl, Synthroid)
This drug is a hormone replacement used in patients with TSH deficiency. Rapidly inhibits the release of thyroid hormones via a direct effect on the thyroid gland and inhibits the synthesis of thyroid hormones. Iodide also appears to attenuate the cAMP-mediated effects of thyrotropin. In active form, influences growth and maturation of tissues. Involved in normal growth, metabolism, and development. The dose of L-thyroxine replacement is age dependent.
Adult
12.5-50 mcg/d PO; may increase by 25-50 mcg/d q2-4wk, not to exceed 100-200 mcg/d
Pediatric
<6 months: 8-12 mcg/kg/d PO
6-12 months: 6-8 mcg/kg/d PO
1-5 years: 4-6 mcg/kg/d PO
5-10 years: 3-4 mcg/kg/d PO
>10 years: 2-3 mcg/kg/d PO
Cholestyramine and iron may decrease liothyronine absorption (Cytomel); estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands; effect of anticoagulants are increased when administered with liothyronine; activity of some beta-blockers may decrease when patients with hypothyroidism are converted to a euthyroid state; soy-based formulas can significantly reduce thyroid hormone absorption in the intestine
Documented hypersensitivity; uncorrected adrenal insufficiency
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Caution in angina pectoris or cardiovascular disease; periodically monitor thyroid status
Somatropin (Genotropin, Humatrope, Nordotropin, Nutropin, Saizen, TevTropin, Omnitrope)
Primary use of GH is as a hormone replacement in short poorly growing children. Stimulates growth of linear bone, skeletal muscle, and organs. Stimulates erythropoietin, which increases red blood cell mass.
Currently widely available in SC injection form. Adjust dose gradually based on clinical and biochemical responses assessed at monthly intervals, including body weight, waist circumference, serum IGF-1, IGFBP-3, serum glucose, lipids, thyroid function, and whole body dual-energy x-ray absorptiometry. In children, assess response based on height and growth velocity. Continue treatment until final height or epiphysial closure or both have been recorded. Increasing evidence indicates that GH replacement is also beneficial in deficient adults.
Adult
Pediatric
0.18-0.3 mg/kg/wk SC; divide in equal doses to be given 6-7 times/wk
Decreased response to GH may occur with long-term therapeutic use of corticotropin or with daily PO corticosteroid
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Debate surrounds when to start GH replacement in those patients who are deficient because of CNS tumors treated with surgery, radiation, or chemotherapy; although no data suggest that GH increases tumor size or recurrence risk, most pediatric endocrinologists wait until the tumor situation has stabilized for at least 1 y before starting therapy; caution in diabetes; reconstitute with sterile water for injection if administering to newborns
Testosterone (Androderm, AndroGel, Andro-LA, Delatest, Depo-Testosterone)
This is used for induction of puberty in hypopituitary males. In the fully developed male, testosterone patches at 5 mg/d provide the advantage of more even control, although some adolescents are uncomfortable wearing them. Administer low-dose testosterone over 1-2 mo to the prepubertal male with gonadotropin deficiency and microphallus who is embarrassed by the small size or the inability to urinate in a standing position.
Adult
75-150 mg IM q7-10d or 100-200 mg IM q2wk
Pediatric
Starting dose: 25-50 mg IM every am, then increase over the next 2-3 y to typical adult doses of 200 mg q2wk; fully developed adolescents can also use testosterone patches 5 mg qd
May increase effects of anticoagulants
Documented hypersensitivity; severe cardiac or renal disease; benign prostatic hypertrophy with obstruction; males with carcinoma of the breast, undiagnosed genital bleeding
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Anabolic effects may enhance hypoglycemia; monitor hand and wrist every 6 mo to determine rate of bone maturation; caution must be used with androgen gel products so that the drug is not accidentally transferred to other individuals by incidental contact
Conjugated estrogens (Premarin)
This drug is used for initiation of puberty in girls with hypogonadotropism. Continue everyday treatment until breakthrough menstrual bleeding occurs and then initiate cyclical therapy. This can be achieved with any of the various PO contraceptives or the addition of medroxyprogesterone 5 mg to an estradiol regimen during the third wk of every mo with no treatment the last wk. PO contraceptive treatment is easier for patient to follow. Instead of Premarin, ethinyl estradiol (Estrace) can be used.
Adult
Pediatric
Premarin: 0.3 mg PO qod starting dose, increase to 0.3 mg qd; switch patients to cyclic therapy when breakthrough bleeding occurs
Estrace: 0.5-1 mg PO qd starting dose, increase to 1 mg PO qd
Caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease
Documented hypersensitivity; thrombophlebitis; undiagnosed vaginal bleeding
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding or mastodynia; estrogens may cause some degree of fluid retention (exercise caution); prolonged unopposed estrogen therapy may increase risk of endometrial hyperplasia
More on Panhypopituitarism |
| Overview: Panhypopituitarism |
| Differential Diagnoses & Workup: Panhypopituitarism |
 Treatment & Medication: Panhypopituitarism |
| Follow-up: Panhypopituitarism |
| Multimedia: Panhypopituitarism |
| References |
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References
Migliaretti G, Aimaretti G, Borraccino A, et al. Incidence and prevalence rate estimation of GH treatment exposure in Piedmont pediatric population in the years 2002-2004: Data from the GH Registry. J Endocrinol Invest. May 2006;29(5):438-42. [Medline].
Hanna CE, Krainz PL, Skeels MR, Miyahira RS, Sesser DE, LaFranchi SH. Detection of congenital hypopituitary hypothyroidism: ten-year experience in the Northwest Regional Screening Program. J Pediatr. Dec 1986;109(6):959-64. [Medline].
Bates AS, Van't Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. Mar 1996;81(3):1169-72. [Medline].
Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. Aug 4 1990;336(8710):285-8. [Medline].
Twickler TB, Wilmink HW, Schreuder PC, et al. Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency. J Clin Endocrinol Metab. Dec 2000;85(12):4683-9. [Medline].
Hoffman RP. Growth hormone (GH) treatment does not restore endothelial function in children with GH deficiency. J Pediatr Endocrinol Metab. Apr 2008;21(4):323-8. [Medline].
Lanes R, Soros A, Flores K, Gunczler P, Carrillo E, Bandel J. Endothelial function, carotid artery intima-media thickness, epicardial adipose tissue, and left ventricular mass and function in growth hormone-deficient adolescents: apparent effects of growth hormone treatment on these parameters. J Clin Endocrinol Metab. Jul 2005;90(7):3978-82. [Medline].
O'Neal D, Hew FL, Sikaris K, Ward G, Alford F, Best JD. Low density lipoprotein particle size in hypopituitary adults receiving conventional hormone replacement therapy. J Clin Endocrinol Metab. Jul 1996;81(7):2448-54. [Medline].
Matthai SM, Smith CS. Pituitary hypoplasia associated with a single central maxillary incisor. J Pediatr Endocrinol Metab. Sep-Oct 1996;9(5):543-4. [Medline].
Willnow S, Kiess W, Butenandt O, et al. Endocrine disorders in septo-optic dysplasia (De Morsier syndrome)--evaluation and follow up of 18 patients. Eur J Pediatr. Mar 1996;155(3):179-84. [Medline].
Burgner DP, Kinmond S, Wallace AM, et al. Male pseudohermaphroditism secondary to panhypopituitarism. Arch Dis Child. Aug 1996;75(2):153-5. [Medline].
Setian N, Aquiar CH, Galvao JA. Rathke's cleft cyst as a cause of growth hormone deficiency and micropenis. In: Child's Nervous System. Vol 5. 1999:271-3.
Rajaratnam S, Seshadri MS, Chandy MJ, Rajshekhar V. Hydrocortisone dose and postoperative diabetes insipidus in patients undergoing transsphenoidal pituitary surgery: a prospective randomized controlled study. Br J Neurosurg. Oct 2003;17(5):437-42. [Medline].
Borchert M, Garcia-Filion P. The syndrome of optic nerve hypoplasia. Curr Neurol Neurosci Rep. Sep 2008;8(5):395-403. [Medline].
Rosenbloom AL, Almonte AS, Brown MR, et al. Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene. J Clin Endocrinol Metab. Jan 1999;84(1):50-7. [Medline].
Ward L, Chavez M, Huot C, et al. Severe congenital hypopituitarism with low prolactin levels and age- dependent anterior pituitary hypoplasia: a clue to a PIT-1 mutation. J Pediatr. Jun 1998;132(6):1036-8. [Medline].
Vieira TC, Boldarine VT, Abucham J. Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency. Arq Bras Endocrinol Metabol. Oct 2007;51(7):1097-103. [Medline].
van Aken MO, Lamberts SW. Diagnosis and treatment of hypopituitarism: an update. Pituitary. 2005;8(3-4):183-91. [Medline].
Bettendorf M, Fehn M, Grulich-Henn J, et al. Lymphocytic hypophysitis with central diabetes insipidus and consequent panhypopituitarism preceding a multifocal, intracranial germinoma in a prepubertal girl. Eur J Pediatr. Apr 1999;158(4):288-92. [Medline].
Maghnie M, Genovese E, Sommaruga MG, et al. Evolution of childhood central diabetes insipidus into panhypopituitarism with a large hypothalamic mass: is 'lymphocytic infundibuloneurohypophysitis' in children a different entity?. Eur J Endocrinol. Dec 1998;139(6):635-40. [Medline].
Mikami-Terao Y, Akiyama M, Yanagisawa T, et al. Lymphocytic hypophysitis with central diabetes insipidus and subsequent hypopituitarism masking a suprasellar germinoma in a 13-year-old girl. Childs Nerv Syst. Mar 25 2006;[Medline].
Tanriverdi F, Senyurek H, Unluhizarci K, et al. High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and at 12-months after the trauma. J Clin Endocrinol Metab. Mar 7 2006;[Medline].
Behan LA, Phillips J, Thompson CJ, Agha A. Neuroendocrine disorders after traumatic brain injury. J Neurol Neurosurg Psychiatry. Jul 2008;79(7):753-9. [Medline].
Acerini CL, Tasker RC, Bellone S, Bona G, Thompson CJ, Savage MO. Hypopituitarism in childhood and adolescence following traumatic brain injury: the case for prospective endocrine investigation. Eur J Endocrinol. Nov 2006;155(5):663-9. [Medline].
Abdu TA, Elhadd TA, Neary R, Clayton RN. Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J Clin Endocrinol Metab. Mar 1999;84(3):838-43. [Medline].
Streeten DH. Shortcomings in the low-dose (1 microg) ACTH test for the diagnosis of ACTH deficiency states. J Clin Endocrinol Metab. Mar 1999;84(3):835-7. [Medline].
Chanoine JP, Rebuffat E, Kahn A, et al. Glucose, growth hormone, cortisol, and insulin responses to glucagon injection in normal infants, aged 0.5-12 months. J Clin Endocrinol Metab. Oct 1995;80(10):3032-5. [Medline].
Fischli S, Jenni S, Allemann S, et al. Dehydroepiandrosterone sulfate in the assessment of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. Feb 2008;93(2):539-42. [Medline].
Carel JC, Tresca JP, Letrait M, et al. Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Metab. Jul 1997;82(7):2117-21. [Medline].
Marin G, Domene HM, Barnes KM, et al. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab. Aug 1994;79(2):537-41. [Medline].
DeVile CJ, Stanhope R. Hydrocortisone replacement therapy in children and adolescents with hypopituitarism. Clin Endocrinol (Oxf). Jul 1997;47(1):37-41. [Medline].
Charmandari E, Lichtarowicz-Krynska EJ, Hindmarsh PC, et al. Congenital adrenal hyperplasia: management during critical illness. Arch Dis Child. Jul 2001;85(1):26-8. [Medline].
Further Reading
Keywords
panhypopituitarism, pituitary gland, inadequate anterior pituitary hormone production, absent anterior pituitary hormone production, congenital anterior hypopituitarism, micropenis, hypoglycemia, poor growth, short stature, delayed puberty, interrupted puberty
