SEVERE ANTERIOR
PITUITARY DEFICIENCY OR PANHYPOPITUITARISM
Severe symptoms of anterior pituitary insufficiency appear only when destruction of the adenohypophysis is nearly complete. With progressive destruction (75%), mild hypogonadism becomes more severe, and general symptoms attributable to thyroid and adrenal cortical hypofunction, such as asthenia, fatigue, loss of appetite, and cold intolerance, appear and progress. Complete anterior pituitary failure may occur after surgery for a pituitary macroadenoma.
Atrophy of the gonads is a constant
finding in this disease. A regression of secondary sexual characteristics also
occurs. In women, the ovaries become small and fibrous, and the uterus regresses
to infantile proportions with an extremely thin layer of endometrium. The
external genitalia shrink, as does the vagina, which develops a smooth,
atrophic epithelium. The breasts regress, and the areolae lose pigmentation. In
men, the penis is small, the testes are shrunken and devoid of rugae, and the
prostate is markedly atrophied. In both sexes, the thyroid gland is small, with
follicles lined with low cuboidal epithelium. Shrinkage of the adrenal cortex
is most obvious in the zona fasciculata and zona reticularis. The zona
glomerulosa, which is the site of aldosterone production, does not depend on
corticotropin (adrenocorticotropic hormone [ACTH]) secretion, in contrast to
the other two layers. The general architectural pattern of the adrenal cortex
is maintained, but the cells are poor in lipid content.
Pallor that is not proportional to
the moderate anemia is typically present and is probably attributable to a
deficiency of ACTH and melanocyte-stimulating hormone. There is a loss of muscle
mass—although multifactorial, the lack of growth hormone (GH) is a main
contributor. Children have a tendency to have hypoglycemia, which is associated
with deficiency of adrenal glucocorticoids as well as lack of GH together with
poor food intake.
The term panhypopituitarism should
be reserved for cases in which all the functions of the adenohypophysis and
neurohypophysis are affected. Patients with slowly progressive destructive
lesions of this region may first manifest diabetes insipidus (DI), which
disappears when involvement of the adenohypophysis becomes extreme enough to
cause secondary adrenal cortical insufficiency. This antagonism between
vasopressin and glucocorticoids is further demonstrated by the reappearance of
DI when these patients are treated with replacement doses of cortisol.
The treatments for ACTH, thyrotropin
(thyroid- stimulating hormone [TSH]), luteinizing hormone (LH), and
follicle-stimulating hormone (FSH) deficiencies are the same as the treatments
for primary deficiencies of the respective target glands. For example, for ACTH
deficiency, hydrocortisone (or other glucocorticoid) is administered to mimic
the normal pattern of cortisol secretion with regard to timing and amount, and
the patient is instructed on the need for higher doses in times of illness and
other stresses. The goal of therapy is resolution of signs and symptoms of
adrenal insufficiency and avoidance of excess glucocorticoid effect (e.g.,
Cushing syndrome).
Patients with TSH deficiency are
treated with levothyroxine. The goal of therapy is a mid-normal serum free
thyroxine concentration. In patients with panhypopituitarism, levothyroxine
should not be administered until
glucocorticoid replacement has been initiated.
Treatment of patients with LH and
FSH deficiency depends on whether fertility is desired. In men, transdermal
testosterone replacement is the treatment of choice for those not interested in
fertility. The dosage of testosterone is adjusted for mid-normal blood
testosterone concentrations. If fertility is desired, men are treated with gonadotropins.
Women can be treated with estrogen-progestin replacement therapy. Women who
wish to become fertile can undergo ovulation induction.
Although the role for GH replacement
in children with hypopituitarism is clear, GH replacement in adults is optional.
Adults with GH deficiency can be treated with GH to optimize body fat, muscle
mass, bone mineral density, and a sense of well-being. The
dosage of GH is titrated to reach a mid-normal insulinlike growth factor 1
concentration.
The only symptom related to
prolactin deficiency is the inability to breastfeed. Recombinant human prolactin
for the treatment of lactation insufficiency is in development.
Patients with diabetes insipidus can
be treated with desmopressin—a two–amino acid modification of vasopressin that
has potent antidiuretic but no vasopressor activity. The goals of therapy are
to reduce nocturia to provide adequate sleep and to control excess urination
during the day. Desmopressi can be administered as a nose spray or an oral tablet.
