Page 767 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster
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PITUITARY CUSHING SYNDROME Adrenocortical Hyperfunction (Hyperadrenalism) 753
ADRENAL CUSHING SYNDROME
Tumor in Cortisol Cortisol
anterior pituitary
ACTH Cortisol
Tumor Nodular hyperplasia
Adrenal hyperplasia IATROGENIC CUSHING SYNDROME
PARANEOPLASTIC CUSHING SYNDROME
ACTH Cortisol Cushing syndrome
Lung cancer Steroids
(or other nonendocrine
Adrenal
cancer) atrophy
Adrenal hyperplasia
Figure 19–35 Schematic representation of the various forms of Cushing syndrome: The three endogenous forms, as well as the more common
exogenous (iatrogenic) form. ACTH, adrenocorticotropic hormone.
many instances the responsible tumor is a small cell carci- MORPHOLOGY
noma of the lung, although other neoplasms, including car-
cinoids, medullary carcinomas of the thyroid, and PanNETs, The main lesions of Cushing syndrome are found in the
have been associated with the syndrome. In addition to pituitary and adrenal glands. The pituitary in Cushing syn-
tumors that elaborate ectopic ACTH, an occasional neuro- drome shows changes that vary with different causes. The
endocrine neoplasm produces ectopic CRH, which in turn most common alteration, resulting from high levels of endog-
causes ACTH secretion and hypercortisolism. As in the enous or exogenous glucocorticoids, is termed Crooke
pituitary variant, the adrenal glands undergo bilateral cor- hyaline change. In this condition, the normal granular,
tical hyperplasia secondary to elevated ACTH, but the basophilic cytoplasm of the ACTH-producing cells in the
rapid downhill course of patients with these cancers often anterior pituitary is replaced by homogeneous, lightly baso-
cuts short the adrenal enlargement. philic material. This alteration is the result of the accumula-
tion of interm ediate keratin filaments in the cytoplasm.
Primary adrenal neoplasms, such as adrenal adenoma and
carcinoma, and rarely, primary cortical hyperplasia, are Morphologic changes in the adrenal glands also depend on
responsible for about 15% to 20% of cases of endogenous the cause of the hypercortisolism and include: (1) cortical
Cushing syndrome. This form of Cushing syndrome is atrophy, (2) diffuse hyperplasia, (3) macronodular or
also designated ACTH-independent Cushing syndrome, or micronodular hyperplasia, or (4) an adenoma or a
adrenal Cushing syndrome, because the adrenals function carcinoma.
autonomously. The biochemical hallmark of adrenal
Cushing syndrome is elevated levels of cortisol with low In patients in whom the syndrome results from exogenous
serum levels of ACTH. In most cases, adrenal Cushing glucocorticoids, suppression of endogenous ACTH results in
syndrome is caused by a unilateral adrenocortical neo- bilateral cortical atrophy, due to a lack of stimulation of
plasm, which may be either benign (adenoma) or malig- the zona fasciculata and zona reticularis by ACTH. The zona
nant (carcinoma). The overwhelming majority of glomerulosa is of normal thickness in such cases, because this
hyperplastic adrenals are ACTH-dependent, and primary portion of the cortex functions independently of ACTH. In
cortical hyperplasia of the adrenal cortices is a rare cause cases of endogenous hypercortisolism, by contrast, the adre-
of Cushing syndrome. There are two variants of this entity; nals either are hyperplastic or contain a cortical neoplasm.
the first presents as macronodules of varying sizes (3 cm Diffuse hyperplasia is found in patients with ACTH-
or greater in diameter) and the second as micronodules dependent Cushing syndrome (Fig. 19–36). Both glands are
(1 to 3 mm). enlarged, either subtly or markedly, each weighing up to
