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- What is the atypical presentation of PPNAD?
PPNAD may present as classical, subclinical, or cyclical Cushing’s syndrome.
In addition, some children with PPNAD may present with “atypical Cushing’s
syndrome” which manifests as asthenia, lean habitus, severe muscle wasting,
short stature, and osteoporosis. Biochemically, 24h urine free cortisol is usually
normal. However, loss of normal diurnal cortisol rhythm and paradoxical
increase in cortisol/UFC following HDDST points towards the diagnosis of
PPNAD.- What is the paradoxical cortisol response to high - dose dexamethasone sup-
pression test?
In response to high-dose dexamethasone, >50 % decline in serum cortisol from
baseline (0800h) cortisol is considered as suppressible HDDST, while failure to
suppress serum cortisol by >50 % from baseline indicates non- suppressible
HDDST. The paradoxical response to dexamethasone is defi ned as >50 % rise
in serum cortisol from baseline cortisol after HDDST during Liddle’s protocol.
PPNAD is the most common cause of paradoxical cortisol response to
HDDST. Rarely, paradoxical response to HDDST may also be seen in patients
with adrenocortical carcinoma. This phenomenon is due to overexpression of
glucocorticoid receptors on adrenal nodules with consequent activation of pro-
tein kinase A signaling pathway, which is involved in cortisol synthesis. - What is Carney ’ s complex?
Carney’s complex is an autosomal dominant disorder and is characterized by car-
dio-cutaneous manifestations and endocrine hyperactivity. The cutaneous manifes-
tations are seen in 80 % and include lentigines, blue nevus, and myxomas. Cardiac
myxomas are present in 30–60 % of patients; usually multiple and can develop in
any cardiac chamber. The most common endocrinopathy associated with Carney’s
complex is Cushing’s syndrome due to PPNAD and is present in 25–60 %, followed
by acromegaly (10 %). Other features of Carney’s complex are testicular tumors,
breast fi broadenoma, ovarian cysts, thyroid tumors, and schwannomas. Inactivating
germline mutations of protein kinase A regulatory subunit 1α-gene (PRKAR 1A)
has been found in 45–65 % of patients with Carney’s complex.- How to monitor a patient with Carney ’ s complex?
In children with Carney’s complex, echocardiography and testicular ultraso-
nography should be performed annually. Growth rate and pubertal development
must be monitored closely in these children for the early detection of endocri-
nopathies. Adolescents and adults with Carney’s complex should be monitored
annually with echocardiography, testicular and thyroid ultrasonography, serum
IGF1, and late-night salivary/midnight serum cortisol.4 Childhood Cushing’s Syndrome