Endocrine tests showed that the sister of our patient also presented PPNAD requiring bilateral adrenalectomy and a similar histopathological pattern was observed. [ncbi.nlm.nih.gov]

Clinical description Although the majority of cases are diagnosed in the 2nd and 3rd decades of life, a substantial proportion of patients present during early childhood (2-3 years). [orpha.net]

• Easy Bruising

  Easy bruising, facial plethora and proximal myopathy are the most sensitive features of Cushing’s syndrome. [clinicaladvisor.com]

  Cushing’s syndrome in Carney complex is always due to primary pigmented nodular adrenocortical disease (PPNAD), and symptoms may be a combination of weight gain, high blood pressure, diabetes, and easy bruising, caused by the overproduction of the hormone [cancer.net]

• Camping

  The stimulatory effect of dexamethasone on cortisol release was not reduced by the adenylyl cyclase inhibitor SQ22536 or potentiated by the phosphodiesterase inhibitor IMBX and the cAMP analog 8Br-cAMP. [ncbi.nlm.nih.gov]

• Short Stature

  As the clinical presentation of Cushing syndrome in this group of patients may be atypical (severe osteoporosis or short stature), the detection of multiple, small adrenocortical nodules with CT or MR imaging supports, or may even suggest, the diagnosis [ncbi.nlm.nih.gov]

  Patients with PPNAD often present with atypical CS, which is characterized by an asthenic, rather than obese, body habitus caused by severe osteoporosis, short stature and severe muscle and skin wasting. [orpha.net]

  The clinical presentation of CS in this group of patients may be atypical, with common manifestations including an asthenic body habitus, short stature, severe osteoporosis, and severe muscle and skin wasting [ 2 ]. [doi.org]

• Infertility

  PPNAD-associated adenomas can cause virilization and infertility by adrenal androgen overproduction. This may be due to steroidogenic control mechanisms that differ from those described for PPNAD without large adenomas. [ncbi.nlm.nih.gov]

  The hormonal changes can lead to hirsutism, males developing breast tissue, females no longer having periods and both sexes may become infertile. High cortisol levels can lead to psychological disturbances such as anxiety or depression and insomnia. [en.wikipedia.org]

• Nausea

  She developed headache, nausea and vomiting in Feb, 1990 and was admitted to the department of neurosurgery with diagnosis of Rt. cerebellar hemorrhage. After discharge, she has been followed for treatment of hypertension. [doi.org]

  Hypopituitarism (as above) Opthalmoplegia, cerebrovascular events, second brain tumors are rare complications Medical treatments Ketoconazole: hepatic injury, gynecomastia, gastrointestinal disturbance, edema, skin rash Metyrapone: dizziness, anxiety, nausea [clinicaladvisor.com]

  Clinical picture: "Addisonian" patients show weakness, nausea, and weight loss, and are usually hypotensive (* 110/70 or less) and have other complaints. Like most endocrine patients, the problems are likely to appear "emotional". [pathguy.com]

• Abdominal Pain

  In the past 2 years he gained ~ 50 pounds, during which time he reported intermittent fatigue, vague abdominal pain, and pain in his lower back. There was no history of muscle weakness, hypertension or diabetes. [digitalcommons.hsc.unt.edu]

  Abdominal pain, gallstones, and hyperamylasemia--a clinical dilemma. Minn Med. 1981 Jul; 64(7):401-3, 396. PMID: 6167847. CASS Principal Investigators and their Associates (Linos DA). Circulation. [connects.catalyst.harvard.edu]

• Vomiting

  She developed headache, nausea and vomiting in Feb, 1990 and was admitted to the department of neurosurgery with diagnosis of Rt. cerebellar hemorrhage. After discharge, she has been followed for treatment of hypertension. [doi.org]

• Osteoporosis

  As the clinical presentation of Cushing syndrome in this group of patients may be atypical (severe osteoporosis or short stature), the detection of multiple, small adrenocortical nodules with CT or MR imaging supports, or may even suggest, the diagnosis [ncbi.nlm.nih.gov]

  Patients with PPNAD often present with atypical CS, which is characterized by an asthenic, rather than obese, body habitus caused by severe osteoporosis, short stature and severe muscle and skin wasting. [orpha.net]

  Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. [uniprot.org]

  The clinical presentation of CS in this group of patients may be atypical, with common manifestations including an asthenic body habitus, short stature, severe osteoporosis, and severe muscle and skin wasting [ 2 ]. [doi.org]

• Fracture

  Bone health can deteriorate, leading to an increased fracture risk in people with Cushing's syndrome. PPNAD is unique as it often causes Cushing's at a young age, in children and adolescents. [en.wikipedia.org]

  Incidental findings of an early L1 compression fracture and multiple rib fractures were made; there was no history of trauma. Given her premature osteoporosis, an endocrinology opinion was sought. [edmcasereports.com]

  Diabetes or other Endocrine issues Patients with hypercortisolism are at risk for osteoporosis and fractures. Regular assessment of bone mineral densities and directed therapies for osteoporosis is recommended for long-term treatment plans. F. [clinicaladvisor.com]

  Carney Syndrome Presented as a Pathological Spine Fracture in a 35-Year-Old Male. Am J Case Rep. 2018 Nov 16; 19:1366-1369. PMID: 30442879. Kiriakopoulos A, Linos D. Thyroid paraganglioma: a case series of a rare head and neck tumor. [connects.catalyst.harvard.edu]

  Sagittal CT reconstruction of lumbar spine shows multilevel vertebral endplate depressions with loss of vertebral body height from osteoporotic spine fractures. [doi.org]

• Hyperpigmentation

  Skin changes in Cushing's syndrome include thinning and bruising easily, developing striae and hyperpigmentation at skin folds. [en.wikipedia.org]

  Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Heart Neoplasms Thoracic Neoplasms Neoplasms by Site Heart Diseases Cardiovascular Diseases Abnormalities, Multiple Congenital Abnormalities Skin Abnormalities Melanosis Hyperpigmentation [clinicaltrials.gov]

  No skin hyperpigmentation was observed and an echocardiogram was also unremarkable. There was no thyroid nodule found. Up to this point, right adrenalectomy was planned. [karger.com]

  […] acromegaly due to somatomammotroph hyperplasia and adenomas not dependent on growth hormone–releasing hormone Signs and symptoms Skin: Pigmentation, including blue nevi of the face, lips, sclera, trunk, or genital mucosa Cutaneous myxomas Generalized hyperpigmentation [emedicine.medscape.com]

  Nelson syndrome is characterized by elevated serum ACTH levels, hyperpigmentation, and progressively enlarging pituitary tumors that are often invasive and, in rare cases, may develop into pituitary carcinomas. 35, 48, 49 This incidence has been reported [doi.org]

• Hypertrichosis

  She had truncal obesity, moon facies and mild hypertrichosis, but no hypertension, no striae and no skin pigmentation. Her height Standard Deviation Score (SDS) was below -2. [austinpublishinggroup.com]

  Three sibs had onset around adolescence of moon facies, obesity, hypertrichosis, purple striae, and osteoporosis. [omim.org]

• Suggestibility

  Results of biochemical tests (in three patients tested) suggested the presence of an autonomously functioning adrenocortical neoplasm. However, radiologic examination of the adrenals did not show an adrenal tumor. [ncbi.nlm.nih.gov]

• Insomnia

  High cortisol levels can lead to psychological disturbances such as anxiety or depression and insomnia. Bone health can deteriorate, leading to an increased fracture risk in people with Cushing's syndrome. [en.wikipedia.org]

  Increasing loss of height with kyphosis, neuropsychiatric manifestations (anxiety and insomnia), and reports of significantly decreased bone mineral density ( Table 2 ) led to reevaluation of the patient at the NIH Clinical Center at age 45 yr. [academic.oup.com]

  Symptoms and signs that should alert you to possible Cushingism: truncal obesity with "buffalo hump" ("upper trunk fat") and "moon face" increased appetite insomnia and mental changes (* Cushing's psychosis seems to be treatable using RU486, i.e., mifepristone [pathguy.com]

Further workup was consistent with primary pigmented nodular adrenal disease (PPNAD) without evidence of Carney Complex. A bilateral adrenalectomy was performed and the patient maintained on oral adrenal hormone replacement therapy. [digitalcommons.hsc.unt.edu]

MRI, with CSI, is also highly accurate in the workup of cortisol-secreting adrenal abnormalities. [doi.org]

Management and treatment Bilateral adrenalectomy is the most common treatment for CS due to PPNAD followed by life-long cortisol and mineralocorticoid supplementation. Prognosis Without treatment, CS due to PPNAD can be life-threatening. [orpha.net]

Bilateral adrenalectomy is the treatment of choice. [ncbi.nlm.nih.gov]

If medication is the only therapy, however, discontinuation of treatment will invariably result in recurrence unless another form of treatment, such as radiosurgery, is administered. 50 Most studies regarding medical therapy for treatment of hypercortisolism [doi.org]

Determine the prognosis for carriers and affected individuals. Provide sufficient data for genetic counseling of families with PPNAD and/or Carney Complex. ... [clinicaltrials.gov]

Prognosis Without treatment, CS due to PPNAD can be life-threatening. The documents contained in this web site are presented for information purposes only. [orpha.net]

Distinguishing between the isolated and syndromic variants of myxoma is essential as it has significant implications for patient management, prognosis and family screening. [doi.org]

MRI T1 lower signal intensity than surrounding atrophic adrenal tissue signal drop out demonstrated on out-of-phase imaging T2: lower signal intensity than surrounding atrophic adrenal tissue Treatment and prognosis The treatment of choice is bilateral [radiopaedia.org]

Although rare, PPNAD should always be considered among the possible etiologies of CS, due to the high prevalence of this disease in this age group. [ncbi.nlm.nih.gov]

To further determine the etiology of Cushing’s syndrome and localize the source of excess glucocorticoids production, additional studies were performed. [digitalcommons.hsc.unt.edu]

Etiology More than 90% of reported cases of PPNAD occur as one of the manifestations of Carney complex (CNC; see this term). Although rare, familial cases of isolated PPNAD have also been reported. [orpha.net]

(See Pathophysiology and Etiology.) [emedicine.medscape.com]

Summary Epidemiology The prevalence of endogenous Cushing syndrome (CS; see this term) is estimated at 1/26,000. PPNAD is responsible for less than 2% of cases. PPNAD is more frequent in females, especially after puberty. [orpha.net]

(See Epidemiology and DDx.) While myxomas are usually sporadic, several familial, autosomal dominant conditions that combine lentiginosis and cardiac myxomas have been described. [emedicine.medscape.com]

Cushing's syndrome: epidemiology and developments in disease management. Clin Epidemiol 2015; 7:281–293 [Google Scholar] 8. Steffensen C, Bak AM, Rubeck KZ, Jorgensen JO. Epidemiology of Cushing's syndrome. [doi.org]

Diverse aberrant hormone receptors have been found to be implicated in the regulation of steroidogenesis and pathophysiology of AIMAH. PPNAD can be found alone or in the context of Carney complex, a multiple endocrine neoplasia syndrome. [ncbi.nlm.nih.gov]

Molecular studies of the tumors of the patients will provide additional clues for the pathophysiologic mechanisms leading to PPNAD/Carney complex. [clinicaltrials.gov]

Groussin L, Cazabat L, Rene-Corail F, Jullian E, Bertherat J (2005) Adrenal pathophysiology: lessons from the Carney complex. Horm Res 64(3):132–139 PubMed CrossRef Google Scholar 5. [doi.org]

Related Articles Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene in patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology [cushings-help.com]

A paradoxical rise of urinary free cortisol (UFC) in response to dexamethasone is an early and specific laboratory marker of the disorder, allowing timely bilateral adrenalectomy which may not only prevent severe complications of hypercortisolism, but [jofem.org]

There is some evidence suggesting that statins can prevent osteonecrosis, but it is of note that our patient was never exposed to such treatment ( 19 ). [edmcasereports.com]

Women with Carney complex may be at a high risk for recurrent atrial myxomas that lead to multiple strokes. [22] Early identification of a female patient with Carney complex may facilitate stroke prevention. [emedicine.medscape.com]

The curative rate of PPNAD was about 30% by unilateral adrenalectomy, 60% by sub-total adrenalectomy, and nearly 100% by total adrenalectomy. 9 The Nelson syndrome could be prevented by routine dosage of adrenocor- ticosteroid replacement. 10 One case [124.205.33.103]

Appropriate Prophylaxis and Other Measures to Prevent Readmission. None VII. What's the evidence? Boscaro, M, Arnaldi, G. “Approach to the Patient with Possible Cushing's Syndrome”. J Clin Endocrinol Metab. vol. 94. 2009. pp. 3121-3131. [clinicaladvisor.com]