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  • Partial or complete deficiency of one or any combination of anterior pituitary hormones.

  • Adrenocorticotropic hormone deficiency: reduced adrenal secretion of cortisol and epinephrine; aldosterone secretion remains intact.

  • Growth hormone (GH) deficiency: short stature in children; asthenia, obesity, and increased cardiovascular risk in adults.

  • Prolactin deficiency: postpartum lactation failure.

  • Thyroid-stimulating hormone (TSH) deficiency: secondary hypothyroidism.

  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deficiency: hypogonadism and infertility in men and women.

General Considerations

Hypopituitarism can be caused by either hypothalamic or pituitary dysfunction. Patients with hypopituitarism may have single or multiple hormonal deficiencies. The anterior pituitary hormones are growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The posterior pituitary hormones are oxytocin and arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). When one pituitary hormonal deficiency is discovered, others may be present.

1. Hypopituitarism with mass lesions

Lesions in the hypothalamus, pituitary stalk, or pituitary can cause hypopituitarism. Pituitary adenomas can cause anterior hypopituitarism, particularly when they are large macroadenomas (1 cm or more in diameter). Clinically nonfunctioning pituitary adenomas, rather than functioning pituitary adenomas, are more likely to grow large enough to cause hypopituitarism;they rarely cause diabetes insipidus. Pituitary adenomas are usually sporadic but 5% arise in familial tumor syndromes. Pituitary adenomas most frequently secrete prolactin or (less commonly) GH or ACTH. Other mass lesions include granulomas, such as granulomatosis with polyangiitis (formerly Wegener granulomatosis), tuberculosis, cholesterol granuloma; Rathke cleft cysts; pituitary apoplexy; metastatic carcinomas or hematologic malignancies; aneurysms; and brain tumors (craniopharyngioma, meningioma, dysgerminoma, glioma, chondrosarcoma, chordoma of the clivus). Rare causes include African trypanosomiasis and Langerhans cell histiocytosis.

Lymphocytic hypophysitis is an autoimmune disorder affecting the pituitary gland. It is characterized by infiltration of the infundibulum and pituitary by lymphocytes, macrophages, and plasma cells. Spontaneous lymphocytic hypophysitis is more common in women (71%) and most frequently presents during pregnancy or postpartum. The condition is often associated with other autoimmune conditions, such as systemic lupus erythematosus (SLE) or Hashimoto thyroiditis. Hypopituitarism typically presents with difficulty breastfeeding and amenorrhea due to hypogonadotropic hypogonadism (62%), diabetes insipidus (54%), headache (50%), hypothyroidism (48%), ACTH deficiency (47%), GH deficiency (37%), and hyperprolactinemia (36%), which clinicians often mistake for a prolactinoma. Immune checkpoint inhibitor hypophysitis can be caused by several immunity-enhancing drugs used for cancer therapy. It is particularly common with the anti-CTLA-4 agents ipilimumab and tremelimumab (10–15%) but has also been reported with the anti-PD-1 agents pembrolizumab and nivolumab. Symptoms of hypophysitis develop on average 9 weeks after beginning the medication and as late as 19 months after commencing therapy.

2. Hypopituitarism without mass lesions

Congenital hypopituitarism occurs in syndromes such as septo-optic dysplasia (de Morsier syndrome) and in patients with various gene mutations, such ...

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