Primary pigmented nodular adrenocortical disease (PPNAD) as an underlying cause of symptoms in a patient presenting with hirsutism and secondary amenorrhea: case report and literature review

Abstract

Hypercortisolemia in females may lead to menstrual cycle disturbances, infertility, hirsutism and acne. Herewith, we present a 18-year-old patient, who was diagnosed due to weight gain, secondary amenorrhea, slowly progressing hirsutism, acne and hot flashes. Thorough diagnostics lead to a conclusion, that the symptoms was the first manifestation of primary pigmented nodular adrenocortical disease (PPNAD). All symptoms of Cushing syndrome including hirsutism and menstrual disturbances resolved after bilateral adrenalectomy. Our report indicates that oligo- or amenorrhea, hirsutism, acne in combination with weight gain, growth failure, hypertension and slightly expressed cushingoid features in a young woman requires diagnostics towards hypercortisolemia. Despite PPNAD is a very rare cause of ACTH-independent Cushing syndrome, it has to be taken into consideration, especially when adrenal glands appear to be normal on imaging and paradoxical rise in cortisol level in high-dose dexamethasone test is observed. Unlike in our patient, in vast majority of patients, PPNAD is associated with Carney complex (CC). Therefore, these patients and their first-degree relatives should be always carefully screened for symptoms of PPNAD, CC and genetic mutations of PRKAR1A, PDE11A, and PDE8B genes.

Treatment of Primary Pigmented Nodular Adrenocortical Disease

“…Due to the inhibitory effect of excessive cortisol secretion on ACTH, the dehydroepiandrosterone (DHEAS) of adrenal CS patients were often lower than those of healthy individuals (42). According to previous reports of patients with PPNAD, laboratory results showed frequent decreases in serum DHEAS levels (25)，and some patients showed overproduction of testosterone and normal DHEAS (24). Overproduction of androgens by PPNAD-associated adenomas leading to virilization and infertility has also been reported in the previous literature (43).…”

“…In another Chinese PPNAD cases (25 patients), PPNAD patients are more likely to develop osteoporosis than ADA patients (78.3 vs. 48.0%), while there are no differences between PPNAD and PBMAH patients 9 . In addition, some patients are accompanied by hyperandrogenemia, with hirsutism and irregular menstruation as the main symptoms 8 24 25 . In a case series of 6 patients from India, one patient had CS associated with symptoms of hyperandrogenism (hirsutism and irregular menses) 8 .…”

“…CT with slice thickness of 3 mm or less may be helpful for diagnosis 36 . Single-photon emission computed tomography (SPECT-CT) with the use of iodomethyl-norcholesterol (I-131) showed bilateral glands uptake was increased 25 . It supported the diagnosis of PPNAD.…”

“…If patients have severe hypercortisolemia preoperatively, they should receive adrenolytic medications for weeks preoperatively 12 . In the literature, Ketoconazole can as a bridge therapy before surgery 8 25 . It is worth noting that Ketoconazole has potential side effects such as liver enzyme elevation, gastrointestinal discomfort, androgen reduction and pruritus 66 .…”

Distinct clinical picture of Cushing’s syndrome in a patient with Morris’ syndrome — first literature report

“…In women, it may present with menstrual cycle disturbances, mainly oligo-or amenorrhoea. Additionally, overproduction of adrenal androgens leads to hirsutism, acne, and infertility [2], which will not be noticed in CAIS patients, leading to diagnostic difficulties.…”