- Partial or complete deficiency of one or any combination of anterior pituitary hormones.
- Adrenocorticotropic hormone deficiency: reduced adrenal secretion of cortisol, testosterone, and epinephrine; aldosterone secretion remains intact.
- Growth hormone (GH) deficiency: short stature in children; asthenia, obesity, and increased cardiac mortality in adults.
- Prolactin deficiency: inhibition of postpartum lactation.
- Thyroid-stimulating hormone (TSH) deficiency: secondary hypothyroidism.
- Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deficiency: hypogonadism and infertility in men and women.
Hypopituitarism can be caused by either hypothalamic or pituitary dysfunction. Patients with hypopituitarism may have single or multiple hormonal deficiencies (Table 26–1). When one hormonal deficiency is discovered, others may be present.
Table 26–1. Pituitary
Hypopituitarism with mass lesions
Lesions in the hypothalamus, pituitary stalk, or pituitary can cause hypopituitarism. Pituitary adenomas are usually sporadic but are sometimes part of multiple endocrine neoplasia type 1 (MEN 1). Pituitary tumors that arise in MEN 1 usually secrete prolactin (63%), GH (9%), or both (10%) and are more aggressive than sporadic adenomas. Pituitary tumors rarely cause diabetes insipidus. Other types of mass lesions include granulomas (eg, granulomatosis with polyangiitis [formerly Wegener granulomatosis], tuberculosis, cholesterol granuloma), Rathke cleft cysts, apoplexy, metastatic carcinomas, aneurysms, and brain tumors (craniopharyngioma, meningioma, dysgerminoma, glioma, chondrosarcoma, chordoma of the clivus). Postpartum pituitary necrosis (Sheehan syndrome), and African trypanosomiasis are rare causes. Langerhans cell histiocytosis usually presents in youth with diabetes insipidus or hypopituitarism; osteolytic bone lesions are noted on radiographs.
Lymphocytic hypophysitis is an autoimmune disorder that most typically affects peripartum women. It can cause a pituitary mass that mimics a tumor. It usually results in ACTH deficiency but can cause deficiencies in any pituitary hormone. About 25% of cases are associated with other autoimmune conditions, such as systemic lupus erythematosus. Hypophysitis can also be caused by chemotherapeutic drugs (eg, ipilumimab, monoclonal anti-CTLA4 antibodies that enhance immunity).
Hypopituitarism without mass lesions
Congenital hypopituitarism occurs in syndromes such as septo-optic dysplasia (de Morsier syndrome) and in patients with PROP1 and other gene mutations. Cranial radiation, pituitary surgery, encephalitis, hemochromatosis, autoimmunity or coronary artery bypass grafting (CABG) may also cause hypopituitarism. At least one pituitary hormone deficiency develops in about 25–30% of survivors of moderate to severe traumatic brain injury (Glasgow Coma Scale ≤ 13/15) and in about 55% of survivors of aneurysmal subarachnoid hemorrhage. Some degree of hypopituitarism, most commonly GH deficiency and hypogonadotropic hypogonadism, occurs in one-third of ischemic stroke patients. Mitotane, given for adrenal cortical carcinoma, can suppress TSH secretion and cause reversible secondary hypothyroidism. Therapy with exogenous corticosteroids (parenteral, oral, inhaled, or topical) can suppress adrenocorticotropic hormone (ACTH) secretion and causes functional isolated secondary adrenal insufficiency.
Congenital isolated hypogonadotropic hypogonadism can be caused by various gene mutations that control the production or release of gonadotropin-releasing hormone (GnRH), LH, or FSH. Congenital adrenal hypoplasia (see below) is one cause of isolated hypogonadotropic hypogonadism. Congenital adrenal hypoplasia may be autosomal recessive or X-linked (due to a mutation in the DAX 1 gene), resulting in adrenal insufficiency in male infants or children. Prader-Willi syndrome (see below) is a genetic disorder where genes on the paternal chromosome 15 are deleted or unexpressed. The incidence of this disorder is 1:15,000; both sexes are affected equally. Kallmann syndrome (see below) is caused by various gene mutations that impair the development or migration of GnRH-synthesizing neurons from the olfactory bulb to the hypothalamus. Kallmann syndrome is usually sporadic but may be familial and inherited as X-linked recessive (Kal 1), autosomal dominant (Kal 2, 3, 4, 5, or 6), or autosomal recessive (Kal 3, 4, or 6). Kallmann syndrome has an incidence of 1:10,000 males and 1:50,000 females.
Also known as hypogonadotropic hypogonadism, gonadotropin deficiency is caused by insufficiencies in LH and FSH, which cause hypogonadism and infertility. Congenital gonadotropin deficiency is characterized by partial or complete lack of pubertal development. (See discussion of Primary Amenorrhea.) Patients with Kallmann syndrome have hypogonadism and anosmia or hyposmia. Half of these patients have unilateral renal agenesis. Some patients with Kallmann syndrome may also exhibit cryptorchidism, micropenis, color blindness, sensorineural deafness, cerebellar ataxia, cognitive problems, bimanual synkinesis, cleft lip or palate, or high-arched palate. Some affected women have menarche followed by secondary amenorrhea.
Patients with congenital adrenal hypoplasia also have congenital normosmic idiopathic hypogonadotropic hypogonadism. Boys with congenital adrenal hypoplasia who survive beyond childhood usually do not enter puberty as a result of their hypogonadotropic hypogonadism. However, hypogonadotropic hypogonadism and subtle signs of adrenal failure can present in adulthood in males with partial loss-of-function mutations in DAX 1. Patients with Prader-Willi syndrome have variable features of both gonadotropin deficiency and primary gonadal dysfunction; boys have cryptorchidism. Other features of Prader-Willi syndrome can include mental retardation, short stature, hyperflexibility, autonomic dysregulation, cognitive impairment, and hyperphagia with obesity.
Acquired gonadotropin deficiency is characterized by the gradual loss of facial, axillary, pubic, and body hair (more prominent in patients who are also hypoadrenal). Men may note diminished beard growth. Libido is diminished. Women have amenorrhea; men note decreased erections. Most patients are infertile. Androgen deficiency predisposes patients to osteopenia and muscle atrophy. Advancing age, obesity, and ...