|Year : 2020 | Volume
| Issue : 7 | Page : 3759-3761
Yashendu Sarda1, Damodar Shenoy1, Shrinath Shetty2, Sonali Ullal3, Sanyam Katyal3
1 Department of Medicine, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Endocrinology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department of Radiodiagnosis, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
|Date of Submission||07-Feb-2020|
|Date of Decision||13-Mar-2020|
|Date of Acceptance||07-Apr-2020|
|Date of Web Publication||30-Jul-2020|
Dr. Yashendu Sarda
Department of General Medicine, KMC Hospital, Attavar, Mangalore, Karnataka - 575001
Source of Support: None, Conflict of Interest: None
This is a case report of 59 years old male with adrenocorticotropic hormone ACTH-independent macronodular adrenal hyperplasia (AIMAH), which is a rare cause of Cushing's syndrome. He was detected to have adrenal lesions incidentally on imaging. The biochemical evaluation was suggestive of endogenous ACTH-independent Cushing's syndrome. Contrast Enhanced CT of the abdomen done to characterize the lesion was suggestive of bilateral macro-nodular adrenal hyperplasia. There was no evidence of cushingoid features except for type 2 diabetes mellitus suggestive of subclinical Cushing's. He was not planned for any immediate medical/surgical management since metabolic control was achieved with oral anti-diabetics (OADs) and anti-hypertensive medications. He is on regular follow up with well-controlled sugars and blood pressure.
Keywords: ACTH, adrenal hyperplasia, AIMAH, cortisol, DST, subclinical Cushing's, UFC
|How to cite this article:|
Sarda Y, Shenoy D, Shetty S, Ullal S, Katyal S. Lean Cushing's. J Family Med Prim Care 2020;9:3759-61
| Introduction|| |
Adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome. Most of the patients have only mild cortisol production and usually present as bilateral incidentalomas. Multiple bilateral non pigmented enlarged macro nodules (greater than 1 cm) are seen in adrenal glands (each adrenal weighing from 25 to 500 mg) that produce excess cortisol independent of adrenocorticotropic hormone (ACTH) that leads to the development of Cushing's syndrome. In routine practice, diagnosis is based on the clinical presentation, biochemical evaluation and imaging. However, it is confirmed by histopathology of the adrenal tissue. Depending on the amount of cortisol excess management can vary from regular monitoring to surgical resection of the adrenal gland. Recently, it has been attributed secondary to aberrant hormone receptor thereby providing the potential for pharmacological therapies.
| Case Report|| |
59 year old male presented with complaints of nocturia from the past 3 months. There was no history of fever with chills, dysuria, dribbling after micturition, increased urgency or hematuria. He was known to have type 2 diabetes mellitus and hypertension that was well controlled on oral anti-diabetics (OADs) and anti-hypertensive agents. He had a history of diabetic ischemic mononeuropathy of the left lateral rectus which was managed conservatively. There was no history of allergy and substance abuse. Historically there was no complaint of osteoporotic fracture, depression, weight gain, irritability, or fatigue.
On physical examination, patient's weight was 66 kg, BMI 25.14 kg/m2, pulse rate of 80 beats per minute, blood pressure of 140/90 mmHg. Systemic examination was inconclusive.
On evaluation, his blood reports showed HbA1C of 5.7%, Na-134 meq/L, K- 4.83 meq/L, Complete blood count, fasting lipid profile, and urine analysis were otherwise normal. Ultrasonography of the abdomen revealed bilateral grade-I renal parenchymal changes, prostatomegaly (45 g, postvoid residual volume 15 mL), fatty liver, and enlarged right adrenal gland (3 cm × 2.2 cm). In view of adrenal incidentaloma, the patient was further subjected to contrast-enhanced computed tomography (CECT) of the abdomen. As described in the image below CECT of the abdomen showed bilaterally enlarged adrenals with multiple nodules-”likely macronodular adrenal hyperplasia possibility of AIMAH [Figure 1] and [Figure 2].
|Figure 1: Axial Post contrast : Bilateral grossly enlarged adrenal glands (Arrows)|
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|Figure 2: Coronal Post contrast: Grossly enlarged bilateral adrenal glands (Arrows) with multiple hypodense nodules and predominant peripheral enhancement|
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Further biochemical evaluation was done to confirm the diagnosis of AIMAH. Morning serum cortisol was elevated, which ruled out exogenous consumption of glucocorticoids[Table 1].
After exogenous glucocorticoid consumption was ruled out, diagnostic tests were done to confirm hypercortisolism. The following three tests are commonly used.,, The patient had elevated midnight cortisol, 24-h urine free cortisol (UFC) and lack of cortisol suppression after 1 mg dexamethasone suppression test (DST) [Table 2].
Once endogenous Cushing's was confirmed, morning and midnight ACTH levels were done to look for ACTH-independent Cushing's syndrome. As both the values were low, a diagnosis of ACTH-independent Cushing's was made [Table 3].
|Table 3: Evaluation for ACTH dependent vs ACTH independent Cushing's syndrome|
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Plasma metanephrines level was normal, which ruled out pheochromocytoma/paragangliomas.
| Discussion|| |
Endogenous Cushing's syndrome secondary to AIMAH is extremely rare, comprising less than 1% of all the cases. This clinical entity has a bimodal age distribution. Few patients present during the 1st decade of life, associated with McCune-Albright syndrome More Details but most of the cases present during the 5th and 6th decade. It is more prevalent in middle-aged women. Usually, patients present with Cushingoid features like obesity, facial plethora, moon face, purple striae, proximal muscle atrophy and skin pigmentation. But our patient is a rare case of subclinical Cushing's syndrome in which there was endogenous hypercortisolism independent of ACTH levels without any overt signs or symptoms of hypercortisolism. Hypertension and diabetes can be attributed secondary to hypercortisolism. The diagnosis is made using biochemical tests and imaging; which is confirmed by biopsy.
The treatment of AIMAH depends on the severity of hypercortisolism. In patients with mild cortisol excess, yearly biochemical assessment and CT scans are sufficient, in the case of disease progression steroid synthesis inhibitors like ketoconazole or even adrenalectomy can be considered. For patients with moderate to severe life-threatening hypercortisolism surgical resection of one or both the adrenals with postoperative hormonal supplementation is the treatment of choice.,,, Recently, it has been revealed that most of the patients with AIMAH and Cushing's syndrome have aberrant cortisol response to various endogenous hormones like vasopressin, gastric inhibitory polypeptide, serotonin, luteinizing hormone/beta–HCG, etc., suggesting the presence of aberrant ectopic receptors. These patients can be treated with a pharmacological antagonist with regular monitoring of UFC levels.,,,, Our patient with subclinical Cushing's syndrome is on regular follow up and biochemical monitoring.
| Conclusion|| |
Patients presenting with common illness may have underlying rare disorders, which can be diagnosed if evaluated carefully. A systematic approach as discussed in our case report helped us recognize a rare cause of Cushing's syndrome. Treatment of patients with subclinical Cushing's is based on the degree of hypercortisolism. Imaging and biochemical assessment should guide the further course of management.
Adrenal incidentalomas are not routinely evaluated, but in a patient with multiple comorbidities like diabetes, hypertension, obesity, and osteoporosis, a thorough workup can help us to diagnose rare treatable conditions like AIMAH.
As primary care providers, we come across patients with hyperglycemia who are treated as insulin resistant Diabetes. But as we all know, most of the clinical features like obesity, dyslipidemia, osteoporosis, and hypertension overlap between Type 2 diabetes mellitus and Cushing's syndrome; it is desirable to do at least one cortisol value and rule out a treatable condition like Cushing's syndrome.
Department of Medicine Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal.
Ethical clearance was obtained from the institutional ethical committee, Kasturba Medical College, Mangaluru (Reg no ECR/541/inst/KA/2014/RR-17).
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his clinical information to be reported in the journal. The patient understand that their names and initials will not be published and due efforts will be made to conceal his identity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hamajima T, Maruwaka K, Homma K, Matsuo K, Fujieda K, Hasegawa T. Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome. Endocr J 2010;57:819-24.
Lacroix A. ACTH-independent macronodular adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009;23:245-59.
Costa MHS, Lacroix A. Cushing's syndrome secondary to ACTH-independent macronodular adrenal hyperplasia. Arq Bras Endocrinol Metabol 2007;51:1226-37.
Fraser LA, Van Uum S. Work-up for Cushing syndrome. CMAJ 2010;182:584-7.
Nieman LK, Biller BMK, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al
. The diagnosis of Cushing's syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:1526-40.
John M, Lila AR, Bandgar T, Menon PS, Shah NS. Diagnostic efficacy of midnight cortisol and midnight ACTH in the diagnosis and localisation of Cushing's syndrome. Pituitary 2010;13:48-53.
Mohammadi S M, Malekzadeh G. A Case of Adrenocorticotropin -Independent Macronodular Adrenal Hyperplasia (AIMAH)- A Case Report. IJDO.2019;11:76-8.
Debillon E, Velayoudom-Cephise FL, Salenave S, Caron P, Chaffanjon P, Wagner T, et al
. Unilateral adrenalectomy as a first-line treatment of Cushing's syndrome in patients with primary bilateral macronodular adrenal hyperplasia. J Clin Endocrinol Metab 2015;100:4417-24.
Osswald A, Quinkler M, Di Dalmazi G, Deutschbein T, Rubinstein G, Ritzel K, et al
. Long-term outcome of primary bilateral macronodular adrenocortical hyperplasia after unilateral adrenalectomy. J Clin Endocrinol Metab 2019;104:2985-93.
Lacroix A, Ndiaye N, Tremblay J, Hamet P. Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome. Endocr Rev 2001;22:75-110.
Bertherat J, Contesse V, Louiset E, Barrande G, Duparc C, Groussin L, et al
. In Vivo
and in Vitro
screening for illegitimate receptors in adrenocorticotropin-independent macronodular adrenal hyperplasia causing Cushing's syndrome: Identification of two cases of gonadotropin/gastric inhibitory polypeptide-dependent hypercortisolism. J Clin Endocrinol Metab 2005;90:1302-10.
Libé R, Coste J, Guignat L, Tissier F, Lefebvre H, Barrande G, et al
. Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: A frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome. Eur J Endocrinol 2010;163:129-38.
Lacroix A, Baldacchino V, Bourdeau I, Hamet P, Tremblay J. Cushing's syndrome variants secondary to aberrant hormone receptors. Trends Endocrinol Metab 2004;15:375-82.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]