Nelson’s syndrome

Nelson’s syndrome

Nelson’s syndrome is a rare and challenging neuroendocrine disorder, and it is associated with elevated Adrenocorticotropic hormone (ACTH) level, skin hyperpigmentation, and pituitary adenoma growth.

Key concepts

● a rare condition that follows 10–30% of total bilateral adrenalectomies (TBA) performed for Cushing’s disease.

● classic triad: hyperpigmentation (skin &mucus membranes), abnormal ↑ ACTH, and progression of pituitary tumor (the last criteria is now controversial)

● treatment options: surgery (transsphenoidal or transcranial), XRT, medication.

Usually occurs 1–4 years after TBA (range: 2 mos-24 years) 1). Theoretical explanation (unproven) 2): following TBA, hypercortisolism resolves, and CRH levels increase back to normal from the (reduced) suppressed state; corticotroph adenomas in patients with NS have an increased & prolonged response to CRH resulting in increased growth. Also, corticotrophs in NS and CD show reduced inhibition by glucocorticoids. It is controversial if some cases may be related to insufficient glucocorticoid replacement after TBA 3).

Clinical features

1. hyperpigmentation (due to melanin stimulating hormone (MSH) cross reactivity of ACTH and actual increased levels of MSH due to increased proopiomelanocortin production). Often the earliest sign that Nelson’s syndrome is developing. Look for linea nigra (midline pigmentation from pubis to umbilicus) and hyperpigmentation of scars, gingivae, and areolae. DDx of hyperpigmentation includes: primary adrenal insufficiency (high levels of ACTH), ectopic ACTH secretion, hemochromatosis (more bronze color), jaundice (yellowish)

2. tumor growth →increased mass effect or invasion: the most serious consequence. These corticotroph tumors are among the most aggressive of pituitary tumors 4). May produce any of the problems associated with macroadenomas (optic nerve compression, cavernous sinus invasion, pituitary insufficiency, H/A, bony invasion…) as well as necrosis with precipitous intracranial hypertension 5); see pituitary apoplexy.

3. malignant transformation of the corticotroph tumor (very rare).

4. hypertrophy of adrenal tissue rests: may be located in the testes → painful testicular enlargement and oligospermia. Rarely the rests can secrete enough cortisol to normalize cortisol levels or even cause a recurrence of Cushing’s disease despite the adrenalectomy.

Diagnosis

1. Laboratories

a) ACTH > 200 ng/L (usually thousands of ng/L)(normal:usually < 54 ng/L)

b) exaggerated ACTH response to CRH (not required for diagnosis)

c) other pituitary hormones may be affected as with any macroadenoma causing mass effect and endocrine screening should be done

2. Formal visual field testing: should be done in patients with suprasellar extension or in those being considered for surgery (as a baseline for comparison)

Treatment

Management options including resection and medical therapy are traditional approaches. Ionizing radiation in the form of Gamma Knife radiosurgery (GKRS) is also being utilized to treat Nelson’s syndrome. In a study Cordeiro et al., sought to better define the therapeutic role of stereotactic radiosurgery (SRS) in Nelson’s syndrome.

Study patients with Nelson’s syndrome were treated with single-fraction GKRS (median margin dose of 25 Gy) at 6 different centers as part of an International Radiosurgery Research Foundation (IRRF) investigation. Data including neurological function, endocrine response, and radiological tumor response were collected and sent to the study-coordinating center for review. Fifty-one patients with median endocrine and radiological follow-ups of 91 and 80.5 months from GKRS, respectively, were analyzed for endocrine remission, tumor control, and neurological outcome. Statistical methods were used to identify prognostic factors for these endpoints.

At last follow-up, radiological tumor control was achieved in 92.15% of patients. Endocrine remission off medical management and reduction in pre-SRS ACTH level were achieved in 29.4% and 62.7% of patients, respectively. Improved remission rates were associated with a shorter time interval between resection and GKRS (p = 0.039). Hypopituitarism was seen in 21.6% and new visual deficits were demonstrated in 15.7% of patients.

GKRS affords a high rate of pituitary adenoma control and improvement in ACTH level for the majority of Nelson’s syndrome patients. Hypopituitarism is the most common adverse effect from GKRS in Nelson’s syndrome patients and warrants longitudinal follow-up for detection and endocrine replacement 6).

References

1) , 3)

Banasiak MJ, Malek AR. Nelson syndrome: comprehensive review of pathophysiology, diagnosis, and management.Neurosurg Focus.2007;23
2)

Assie G, Bahurel H, Coste J, Silvera S, Kujas M, Dugue MA, et al. Corticotroph tumor progression after adrenalectomy in Cushing’s Disease: a reappraisal of Nelson’s syndrome. J Clin Endocrinol Metab. 2007; 49:381–386
4)

Bertagna X, Raux-Demay M-C, Guilhaume B, et al., Melmed S. In: Cushing’s Disease. The Pituitary. 2nd ed. Malden, MA: Blackwell Scientific; 2002:496–560
5)

Kasperlik-Zaluska AA, Bonicki W, Jeske W, Janik J, et al. Nelson’s syndrome – 46 years later: clinical experience with 37 patients. Zentralbl Neurochir. 2006; 67:14–20
6)

Cordeiro D, Xu Z, Li CE, Iorio-Morin C, Mathieu D, Sisterson ND, Kano H, Attuati L, Picozzi P, Sheehan KA, Lee CC, Liscak R, Jezkova J, Lunsford LD, Sheehan J. Gamma Knife radiosurgery for the treatment of Nelson’s syndrome: a multicenter, international study. J Neurosurg. 2019 Jul 12:1-6. doi: 10.3171/2019.4.JNS19273. [Epub ahead of print] PubMed PMID: 31299652.

Morquio syndrome

Morquio syndrome

Morquio’s syndrome (referred to as mucopolysaccharidosis IV or Morquio’s) is an autosomal recessive mucopolysaccharide storage disease (see also lysosomal storage disorder), usually inherited.

It is a rare type of birth defect with serious consequences. When the body cannot process certain types of mucopolysaccharides, they build up or are eliminated, causing various symptoms. These involve accumulation of keratan sulfate.

Classification

This syndrome has two forms, A and B, referred to as Morquio A and Morquio B syndrome or MPS IVA and MPS IVB. The two forms are distinguished by the gene product involved; Type A involves a malfunction in the GALNS gene, while Type B involves a malfunction of the GLB1 gene.

Type A GALNS Missing enzyme: Galactosamine-6 sulfatase Chromosomal region: 16q24

Type B GLB1 Missing enzyme: Beta-galactosidase Chromosomal region: 3p22

Treatment

Complications

Craniovertebral junction anomaly and C1-C2 instability resulting in myelopathy have been well described in the literature.

Spinal involvement in MPS-IV patients, with neurological impairment, other than atlanto-axial instability and thoracolumbar kyphosis, has been scarcely mentioned in the literature.

Neurological problems secondary to progressive kyphosis and stenosis at the cervicothoracic and upper thoracic spine are seen in children with Morquio syndrome. Early detection with a careful neurological assessment, whole spine MR imaging, and appropriate surgical treatment can prevent permanent neurological sequelae 1).

Case reports

The records of patients with syndromic Craniovertebral Junction Anomaly treated by Muthukumar during the period of 2012-2017 were retrospectively reviewed. Patients in whom intraoperative difficulties and complications were encountered were culled out from the database. Complications were divided into (1) technique related, (2) neural injury, (3) vascular injury, (4) instrumentation pull out/breakage, (5) screw misplacement and, (6) where postoperatively, the surgeon felt an alternate surgical technique could have yielded better results. Four patients with either unexpected intraoperative difficulties or complications or in whom the technique could have been refined were identified. There were 2 patients with proatlas segmentation anomalies and 2 with Morquio syndrome. The first patient had cage migration which necessitated a second procedure during craniovertebral realignment, the second had partial penetration of the screw into the transverse foramen, the third with bipartite atlas underwent a C1-2 fixation without a horizontal cross-connector and, the fourth had screw pull outs from the subaxial cervical spine intraoperatively during an attempted occipitocervical fusion. In children with syndromic CVJ anomalies, the surgeon should be aware of the high risk of intraoperative difficulties and complications. Potential pitfalls and the ways to avoid these complications are discussed 2).

References

1)

Baratela WA, Bober MB, Thacker MM, Belthur MV, Oto M, Rogers KJ, Mackenzie WG. Cervicothoracic myelopathy in children with morquio syndrome a: a report of 4 cases. J Pediatr Orthop. 2014 Mar;34(2):223-8. doi: 10.1097/BPO.0000000000000074. PubMed PMID: 24096444.
2)

Muthukumar N. Problems in Instrumentation of Syndromic Craniovertebral Junction Anomalies – Case Reports. Neurospine. 2019 Jun;16(2):277-285. doi: 10.14245/ns.1938176.088. Epub 2019 Jun 30. PubMed PMID: 31261467.

Hubris syndrome in neurosurgery

Hubris syndrome

Hubris syndrome (HS) is an acquired psychiatric disorder that affects people who exercise power in any of its forms. It has been reported in many fields, from politics to finance. The physician-patient relationship is also one of power. A lack of humbleness and empathy in this situation can lead to qualities such as self-confidence and self-assurance becoming pride, arrogance and high-handedness, which characterise a doctor suffering from HS.

The diagnostic criteria for HS initially reported in political leaders with government responsibilities are analysed and transferred to the medical field of neurosurgery. Two forms of medical HS are described and ten diagnostic criteria are proposed that are valid for any physician-patient relationship.

HS is an acquired psychiatric disorder that is triggered by power and enhanced by success, and can easily be observed on a daily basis in physicians working in settings that are very close to us. Early identification of these medical behaviours is necessary to be able to mitigate their consequences 1).

1)

Gonzalez-Garcia J. [Hubris syndrome in neurosurgery]. Rev Neurol. 2019 Apr 16;68(8):346-353. doi: 10.33588/rn.6808.2018355. Review. Spanish. PubMed PMID: 30963532.
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