primary pigmented nodular adrenocortical disease 2

Primary Pigmented Nodular Adrenocortical Disease (PPNAD) Description

PPNAD is a rare but important cause of hypercortisolism, particularly in the pediatric age group. It is characterized by multiple small and pigmented nodules in the adrenal cortex [2]. These nodules are typically less than 1 cm in diameter and can be found in both normal-sized and enlarged adrenal glands [3].

The disease is a form of ACTH-independent adrenal hyperplasia, resulting in Cushing syndrome. PPNAD can also be combined with other conditions, such as the "complex of myxomas, spotty pigmentation, and endocrine tumors" (CMPS) [5]. On histology, PPNAD is characterized by multiple non-encapsulated adrenocortical nodules varying in size from less than 1 mm to 30 mm [7].

PPNAD is a rare syndrome that involves the formation of abnormal tumors causing endocrine hyperactivity. It can be isolated or part of a complex syndrome, and its exact cause remains unknown [4].

Common Signs and Symptoms of Primary Pigmented Nodular Adrenocortical Disease (PPNAD)

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare condition that affects the adrenal glands, leading to an overproduction of cortisol. The signs and symptoms of PPNAD can vary from person to person but often include:

• Weight gain in the face and upper body: This is one of the most common symptoms of PPNAD, where people experience weight gain in the midsection, face, and upper body (1).
• Slowed growth in children: In children, PPNAD can cause slowed growth and development (5).
• Fragile skin: People with PPNAD may have fragile skin that is prone to bruising or tearing (5).
• Fatigue: Fatigue is a common symptom of PPNAD, which can be severe in some cases (5).
• Obesity: Obesity is another common sign of PPNAD, particularly around the midsection (9).
• Striae: Striae, also known as stretch marks, can appear on the skin due to the excess cortisol production (9).
• Weakness: Muscle weakness and fatigue are common symptoms of PPNAD (9).
• Osteoporosis: Osteoporosis is a risk in people with PPNAD due to the high levels of cortisol, which can lead to bone loss (9).
• Hypertension: High blood pressure is another potential complication of PPNAD (9).
• Diabetes: Some people with PPNAD may develop diabetes due to the excess cortisol production (9).

It's essential to note that these symptoms can vary in severity and may not be present in all individuals with PPNAD. If you suspect you or a loved one has this condition, consult a healthcare professional for proper diagnosis and treatment.

References: (1) [1] (5) [5] (9) [9]

Diagnostic Tests for Primary Pigmented Nodular Adrenocortical Disease (PPNAD) 2

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare form of bilateral adrenal hyperplasia that can be challenging to diagnose. The diagnostic process typically involves a combination of clinical evaluation, laboratory tests, and imaging studies.

Clinical Evaluation

A thorough clinical evaluation is essential for diagnosing PPNAD 2. This includes:

• Medical history: A detailed medical history should be taken to identify any symptoms or signs that may suggest PPNAD 2.
• Physical examination: A physical examination should be performed to look for any abnormalities in the adrenal glands, such as nodules or tumors.

Laboratory Tests

Several laboratory tests can help diagnose PPNAD 2:

• Corticotropin-releasing hormone (CRH) test: This test measures the level of CRH in the blood and can help determine if there is an overproduction of cortisol.
• High-dose dexamethasone suppression test: This test measures the response of cortisol production to high doses of dexamethasone, which can help diagnose PPNAD 2.
• Adrenal gland computed tomography (CT) scan: A CT scan can help visualize the adrenal glands and identify any nodules or tumors.

Genetic Testing

Genetic testing may also be recommended for individuals suspected to have PPNAD 2:

• Sequence analysis of the entire coding region: This test analyzes the genetic material in the PDE11A gene, which is associated with PPNAD 2.
• CNV detection via next-generation sequencing: This test detects any copy number variations (CNVs) in the PDE11A gene that may be associated with PPNAD 2.

Other Diagnostic Tests

Other diagnostic tests may also be used to confirm the diagnosis of PPNAD 2:

• Adrenal gland biopsy: A biopsy of the adrenal gland can provide a definitive diagnosis.
• Imaging studies: Imaging studies such as MRI or CT scans can help visualize

Treatment Options for Primary Pigmented Nodular Adrenocortical Disease (PPNAD)

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing's syndrome, characterized by the presence of small, pigmented adrenal nodules. While surgical options such as adrenalectomy are available, drug treatment can also be an effective approach for managing this condition.

Medications Used in PPNAD Treatment

Several medications have been reported to be effective in treating PPNAD, including:

• Ketoconazole: This antifungal medication has been shown to inhibit cortisol production and is often used as a preoperative treatment to reduce cortisol levels before surgery [1][3].
• Metyrapone: Another medication that can block cortisol production, metyrapone has been reported to be effective in some patients with PPNAD [1][3].
• Mitotane: Although rarely used, mitotane is another option for treating PPNAD by inhibiting cortisol production [8].

Other Treatment Options

In addition to these medications, other treatment options may include:

• Adrenal imaging: To assess the size and number of adrenal nodules
• Sequential low-dose-high-dose dexamethasone suppression test (Liddle's test): To evaluate cortisol production and response to dexamethasone [6]
• Genetic testing: To identify genetic mutations associated with PPNAD

Recent Advances in PPNAD Treatment

A recent review highlights the clinical features, pathogenic variants, and recent progress in investigation and therapy of PPNAD [7]. This includes a summary of the current treatment options and emerging therapies for this rare condition.

References:

[1] by X Liu · 2022 · Cited by 7 — Medications for hypercortisolemia, such as Ketoconazole, Metyrapone and Mitotane et.al, have been reported as a preoperative transition for in some patients ...

[3] by X Liu · 2022 · Cited by 7 — Medications for hypercortisolemia, such as Ketoconazole, Metyrapone and Mitotane et.al, have been reported as a preoperative transition for in some patients ...

[6] by LK Nieman · Cited by 6 — - Choice of initial agent · Ketoconazole · Levoketoconazole · Metyrapone · Osilodrostat · Mitotane (rarely used) · - Risk of adrenal ...

Differential Diagnosis of Primary Pigmented Nodular Adrenocortical Disease (PPNAD)

Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare cause of Cushing syndrome, and its differential diagnosis involves considering various conditions that can present with similar symptoms. Here are some key points to consider:

• Adrenal tumors: In children below 4 years, the most frequent cause of adrenal enlargement is adrenocortical tumors, followed by bilateral hyperplasia due to McCune-Albright syndrome [6].
• Neoplasms: Adenoma, adrenocortical carcinoma, and other types of neoplasms can also be considered in the differential diagnosis of PPNAD (Table 1) [8].
• Bilateral hyperplasia: McCune-Albright syndrome is a rare genetic disorder that can cause bilateral adrenal hyperplasia, which may present with similar symptoms to PPNAD.
• Other causes: Other conditions such as adrenal hemorrhage, cysts, and metastatic disease should also be considered in the differential diagnosis of PPNAD.

Key Diagnostic Features

To differentiate PPNAD from other conditions, the following features are important:

• Reticulin staining pattern: A short thick, anastomosing reticulin staining pattern can be used for differential diagnosis of endocrine gland lesions in the adrenal gland [5].
• Imaging studies: Imaging studies such as CT or MRI scans can help to identify the presence and characteristics of nodules in the adrenal glands.

References

[1] by G Bavadiya · 2020 · Cited by 2 — Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome in children and it has characteristic gross and microscopic features [1]. [2] by X Liu · 2022 · Cited by 7 — Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome, with characteristic imaging and histopathological features [2]. [3] by GN Zografos · 2010 · Cited by 11 — Even though PPNAD, sporadic or familial, is a rare cause of CS, it should be included in the differential diagnosis of ACTH-independent CS, especially in children and young adults [3]. [4] Aug 1, 1989 — Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in infants, children, and young adults [4]. [5] May 28, 2022 — Reticulin staining pattern can be used for differential diagnosis of endocrine gland lesion in adrenal gland [5]. [6] Jun 15, 2018 — In children below 4 years, the most frequent cause is adrenocortical tumors, followed by bilateral hyperplasia due to McCune-Albright syndrome [6]. [7] by JL Doppman · 1989 · Cited by 139 — Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in infants, children, and young adults [7]. [8] by J Connelly · 2021 — The differential diagnosis for adrenal enlargement is shown in Table 1. 1. Neoplasms. a). Adenoma. b). Adrenocortical carcinoma. c ... [8]. [9] by J Wernig · 2024 — Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome (CS), presenting diagnostic challenges [9].