Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Ceccato, Filippo; Barbot, Mattia; Albiger, Nora; Zilio, Marialuisa; Toni, Pietro De; Luisetto, Giovanni; Zaninotto, Martina; Greggio, Nella Augusta; Boscaro, Marco; Scaroni, Carla; Camozzi, Valentina

doi:10.1530/eje-16-0104

Cited by 35 publications

(42 citation statements)

References 23 publications

(30 reference statements)

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“…Similarly, in children with NCAH, the BMD was normal or at least better than that in children with classic CAH (124). However, other studies found a similar frequency of osteoporosis or decreased BMD in NCAH, compared to classic CAH (6,123,125,126,127). Fracture prevalence has sometimes been reported in CAH (82,121,122,127,128,129) and patients with NCAH have appeared to have fewer fractures than those with classic forms (121,122).…”

Section: Bone Mineral Density and Fracturesmentioning

confidence: 91%

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

Nordenström

Falhammar

2019

European Journal of Endocrinology

115

129

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Non-classic congenital adrenal hyperplasia (NCAH) is a relatively common disorder regardless of ethnicity, but most cases are never diagnosed, especially in males. A baseline 17-hydroxyprogesterone measurement may be used for screening, but 17-hydroxyprogesterone measurement after ACTH stimulation is the gold standard. We advocate a CYP21A2 mutation analysis to verify the diagnosis, for genetic counselling and for better prognostic and treatment guidance. Most patients are diagnosed in adolescence and adult life with hirsutism, acne, a PCOS-like picture and fertility issues. Many men with NCAH never seek medical attention and escape diagnosis. Although treatment is somewhat controversial, an early diagnosis and start of treatment may have positive implications on growth and be relevant for preventing and ameliorating the symptoms and consequences of androgen excess that develop over time, including fertility issues. Long-term treatment with glucocorticoids will improve the androgen symptoms but may result in long-term complications, such as obesity, insulin resistance, hypertension, osteoporosis and fractures. The glucocorticoid doses should be kept low. However, complications seen in NCAH, assumed to be caused by the glucocorticoid treatment, may also be associated with long-term androgen exposure. Oral contraceptive pills are a common treatment option for young females with NCAH. Regular clinical monitoring to improve the clinical outcome is recommended. It is important to acknowledge that glucocorticoid treatment will lead to secondary cortisol insufficiency and the need for stress dosing. Studies focusing on the specific difficulties patients with NCAH face, both those with a late clinical diagnosis and those with a neonatal diagnosis obtained by screening, are warranted.

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Section: Bone Mineral Density and Fracturesmentioning

confidence: 91%

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

Nordenström

Falhammar

2019

European Journal of Endocrinology

115

129

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“…Body composition was measured with DXA in all patients; the same Discovery W Hologic QDR 4500 C densitometer (Hologic Inc., Waltham, MA, USA) was used at baseline (during active hypercortisolism, before any treatment to reduce cortisol levels) and during remission. The mean precision error (coefficient of variation) was 0.6 %; reproducibility was 1.2 % [21]. Total body and trunk/abdominal fat/lean mass were measured by DXA; whereas the R1-box was manually defined as DXA subregion 4 cm (or 3 pixels) slice at the top of iliac crest [22].…”

Section: Body Compositionmentioning

confidence: 99%

Body Composition is Different After Surgical or Pharmacological Remission of Cushing’s Syndrome: A Prospective DXA Study

et al. 2017

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Patients with active Cushing's syndrome (CS) exhibit an increase of the visceral adipose tissue, increasing the risk of cardiovascular events. Until now, it is not yet clear whether remission of CS leads to a normalization of body composition, or if different strategies to control hypercortisolism could result in a different clinical outcome concerning adipose tissue distribution. Therefore, we analyzed body composition changes using dual-energy X-ray absorptiometry (DXA) in patients with CS in a prospective and controlled study. We considered 23 patients with CS, whose remission was achieved after surgery in 14 or gained with pharmacological treatment in 9 subjects. Clinical and DXA data (lean and fat mass in total body, trunk, and R1 box) were collected during active hypercortisolism and after sustained remission, defined as the normalization of both late night salivary and 24-h urinary cortisol levels, at least for 6 consecutive months. Healthy subjects, matched with CS for gender, age, and BMI, were considered as controls (n=25). After remission of hypercortisolism, body compositions of patients were similar to matched controls; fat mass in total body (-7.53%), trunk (-3.24%), and R1- box (-12.82%, all p<0.01) were decreased from baseline levels. Dividing patients by type of treatment, fat mass reduction was higher in those that achieved surgical remission of CS (total body -17.26%, trunk -22.73%, and R1 box -21.21%, all p<0.05). Surgical remission of hypercortisolism is characterized by improvement of body composition, particularly fat reduction, easily detectable with DXA during routine clinical practice.

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“…Prednisolone may be associated with worse BMD than hydrocortisone [95,97,104,105]. Fractures have not been reported in 3βHSD2D so far but may be increased in CAH in general [93,95,97,99,100,103].…”

Section: Bone Mineral Density and Fracturesmentioning

confidence: 93%

“…Only one case of 3βHSD2D and BMD measurements has been reported, and has showed osteoporosis [75]. In general, studies in adults with CAH have demonstrated impaired BMD [4,[93][94][95][96][97][98][99][100], even though there are exceptions with normal BMD [101,102], and better than other DSD conditions [103]. Prednisolone may be associated with worse BMD than hydrocortisone [95,97,104,105].…”

Section: Bone Mineral Density and Fracturesmentioning

confidence: 99%

Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency

2019

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Purpose 3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D) is a very rare variant of congenital adrenal hyperplasia (CAH) causing less than 0.5% of all CAH. The aim was to review the literature. Methods PubMed was searched for relevant articles. Results 3βHSD2D is caused by HSD3B2 gene mutations and characterized by impaired steroid synthesis in the gonads and the adrenal glands and subsequent increased dehydroepiandrosterone (DHEA) concentrations. The main hormonal changes observed in patients with 3βHSD2D are elevated ratios of the Δ5-steroids over Δ4-steroids but molecular genetic testing is recommended to confirm the diagnosis. Several deleterious mutations in the HSD3B2 gene have been associated with saltwasting (SW) crisis in the neonatal period, while missense mutations have been associated with a non-SW phenotype. Boys may have ambiguous genitalia, whereas girls present with mild or no virilization at birth. The existence of non-classic 3βHSD2D is controversial. In an acute SW crisis, the treatment includes prompt rehydration, correction of hypoglycemia, and parenteral hydrocortisone. Similar to other forms of CAH, glucocorticoid and mineralocorticoid replacement is needed for long-term management. In addition, sex hormone replacement therapy may be required if normal progress through puberty is failing. Little is known regarding possible negative long-term consequences of 3βHSD2D and its treatments, e.g., fertility, final height, osteoporosis and fractures, adrenal and testicular tumor risk, and mortality. Conclusion Knowledge is mainly based on case reports but many long-term outcomes could be presumed to be similar to other types of CAH, mainly 21-hydroxylase deficiency, although in 3βHSD2D it seems to be more difficult to suppress the androgens.

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Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Cited by 35 publications

References 23 publications

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

Body Composition is Different After Surgical or Pharmacological Remission of Cushing’s Syndrome: A Prospective DXA Study

Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency

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