Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency

Introduction Pazopanib is an agent that is being successfully used in soft tissue sarcomas. Some endocrine side effects may develop during pazopanib treatment. Here, we presented a case diagnosed with secondary adrenal insufficiency while being investigated for etiology of hypoglycemia which developed after pazopanib. Case report A 69-year-old male patient was operated in June 2019 due to a lung mass 26 × 18 × 10 cm in size. Pathological diagnosis revealed a solitary fibrous tumor with malignant behavior. The patient received three lines of chemotherapy. After pazopanib treatment, a hypoglycemic attack was reported. Management and outcome: Blood cortisol and ACTH (Adrenocorticotropic hormone) levels were not increased at the time of the hypoglycemic attack, and levels of other pituitary hormones were found to be normal. Electrolyte levels were in normal range. Since the counteracting hormone did not reach a sufficient level, it was considered secondary adrenal insufficiency. Hypoglycemic attacks did not occur during follow-up while taking steroid therapy and pazopanib. Discussion A single case of primary adrenal insufficiency has been reported in the literature. We here present a case who developed hypoglycemia after pazopanib and was diagnosed with drug-associated secondary adrenal insufficiency. When hypoglycemia develops during pazopanib treatment, we must be aware of adrenal insufficiency.

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Premature Mortality in Patients with Addison’s Disease: A Population-Based Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0076 ◽

2006 ◽

Vol 91 (12) ◽

pp. 4849-4853 ◽

Cited By ~ 275

Author(s):

Ragnhildur Bergthorsdottir ◽

Maria Leonsson-Zachrisson ◽

Anders Odén ◽

Gudmundur Johannsson

Keyword(s):

Survival Rate ◽

Confidence Interval ◽

Infectious Diseases ◽

Adrenal Insufficiency ◽

Addison’S Disease ◽

Population Based ◽

Addison's Disease ◽

Primary Adrenal Insufficiency ◽

Background Population

Abstract Background: The survival rate of patients with primary adrenal insufficiency (Addison’s disease) undergoing currently accepted replacement therapy is not known, although well-informed patients are considered to have a normal survival rate. In this study, we evaluated the mortality of patients with Addison’s disease in Sweden. Methods: A population-based, retrospective, observational study was performed, using the National Swedish Hospital and Cause of Death Registers, covering the period from 1987–2001. After a diagnosis of Addison’s disease, each patient was followed until the end of follow-up or death. Mortality was compared with that of the Swedish background population. Findings: We identified 1675 patients (995 women and 680 men) diagnosed with primary adrenal insufficiency. The average follow-up from initial diagnosis was 6.5 yr. Five hundred seven patients died during the study period compared with an expected 199. The risk ratio for all-cause mortality was 2.19 (confidence interval 1.91–2.51) for men and 2.86 (confidence interval 2.54–3.20) for women. The excess mortality in both men and women was attributed to cardiovascular, malignant, and infectious diseases. Concomitant diabetes mellitus was observed in 12% of the patients, but only contributed to the increased mortality to a minor extent. Interpretation: Compared with the background population, we observed that the risk ratio for death was more than 2-fold higher in patients with Addison’s disease. Cardiovascular, malignant, and infectious diseases were responsible for the higher mortality rate.

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NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects

Acta Endocrinologica ◽

10.1530/eje-16-0056 ◽

2016 ◽

Vol 175 (1) ◽

pp. 73-84 ◽

Cited By ~ 27

Author(s):

Florence Roucher-Boulez ◽

Delphine Mallet-Motak ◽

Dinane Samara-Boustani ◽

Houweyda Jilani ◽

Asmahane Ladjouze ◽

...

Keyword(s):

Oxidative Stress ◽

Adrenal Insufficiency ◽

Severe Hypoglycemia ◽

Compound Heterozygous ◽

Primary Adrenal Insufficiency ◽

Cell Adenoma ◽

Molecular Etiology ◽

Phenotype Heterogeneity ◽

New Mutations

Objective Nicotinamide nucleotide transhydrogenase (NNT), one of the several genes recently discovered in familial glucocorticoid deficiencies (FGD), is involved in reactive oxygen species detoxification, suggesting that extra-adrenal manifestations may occur, due to the sensitivity to oxidative stress of other organs rich in mitochondria. Here, we sought to identify NNT mutations in a large cohort of patients with primary congenital adrenal insufficiency without molecular etiology and evaluate the degree of adrenal insufficiency and onset of extra-adrenal damages. Methods Sanger or massive parallel sequencing of NNT and patient monitoring. Results Homozygous or compound heterozygous NNT mutations occurred frequently (26%, 13 unrelated families, 18 patients) in our cohort. Seven new mutations were identified: p.Met337Val, p.Ala863Glu, c.3G>A (p.Met1?), p.Arg129*, p.Arg379*, p.Val665Profs*29 and p.Ala704Serfs*19. The most frequent mutation, p.Arg129*, was found recurrently in patients from Algeria. Most patients were diagnosed belatedly (8–18 months) after presenting severe hypoglycemia; others experiencing stress conditions were diagnosed earlier. Five patients also had mineralocorticoid deficiency at onset. One patient had congenital hypothyroidism and two cryptorchidism. In follow-up, we noticed gonadotropic and genitalia impairments (precocious puberty, testicular inclusions, interstitial Leydig cell adenoma, azoospermia), hypothyroidism and hypertrophic cardiomyopathy. Intrafamilial phenotype heterogeneity was also observed. Conclusions NNT should be sequenced, not only in FGD, but also in all primary adrenal insufficiencies for which the most frequent etiologies have been ruled out. As NNT is involved in oxidative stress, careful follow-up is needed to evaluate mineralocorticoid biosynthesis extent, and gonadal, heart and thyroid function.

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Type II polyglandular autoimmune syndrome: a case of Addison’s disease precipitated by use of levothyroxine

BMJ Case Reports ◽

10.1136/bcr-2019-230760 ◽

2019 ◽

Vol 12 (8) ◽

pp. e230760 ◽

Cited By ~ 2

Author(s):

Katherine Hoener ◽

Tulsi Sharma

Keyword(s):

Adrenal Insufficiency ◽

Autoimmune Disorder ◽

Adrenal Crisis ◽

Antibody Treatment ◽

Primary Adrenal Insufficiency ◽

Polyglandular Autoimmune Syndrome ◽

Autoimmune Syndrome ◽

Life Threatening ◽

Endocrinology Clinic

A 46-year-old woman was referred to the endocrinology clinic for evaluation of progressive fatigue, dizziness and treatment-resistant hypothyroidism. Initial laboratory results revealed hypothyroidism, hyponatraemia and hyperkalaemia. Liothyronine sodium (Cytomel) was initiated, which exacerbated her fatigue and dizziness. Suspecting adrenal insufficiency, an 08:00 cortisol level was obtained and found to be low with failure to increase following cosyntropin stimulation test. Diagnosis of primary adrenal insufficiency was confirmed via CT abdomen and pelvis revealing diminutive adrenal glands and elevated 21-hydroxylase antibody. Treatment was initiated with hydrocortisone 10 mg every morning and 5 mg at 16:00/day, with plan for patient follow-up in 3 weeks to assess need for mineralocorticoid replacement. Polyglandular syndromes are rare and have a wide variety of presentation. Thus, we recommend screening patients with a single autoimmune disorder who do not respond to conventional therapy to prevent possible life-threatening adrenal crisis.

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