An unusual case of Cushing’s syndrome due to bihormonal ACTH–prolactin secreting pituitary macroadenoma with rapid response to cabergoline

  1. Shalini Kunasegaran1,2,
  2. Michael S Croxson1,
  3. Ian Holdaway1,
  4. Rinki Murphy1

+Author Affiliations


  1. 1Department of EndocrinologyAuckland District Health BoardAuckland, New Zealand

  2. 2Department of EndocrinologyWaitemata District Health BoardTakapuna, New Zealand
  1. Correspondence to Dr Shalini Kunasegaran, shal84@gmail.com
  • Accepted 13 July 2017
  • Published 7 August 2017

Summary

A 23-year-old man presenting with florid Cushing’s syndrome was found to have high plasma ACTH and very high serum prolactin. Pituitary MRI showed a large invasive macroadenoma.

Low-dose cabergoline promptly suppressed both ACTH and prolactin levels within 2 weeks, with unexpected clinical and biochemical hypocortisolism requiring hydrocortisone replacement. Secondary hypogonadism was reversed. Clinical and biochemical remission of his Cushing’s syndrome together with significant shrinkage of his macroadenoma has been maintained for 1 year on cabergoline 0.5 mg twice weekly. Reduction in pituitary

Reduction in pituitary tumour volume and brisk fall in serum prolactin in response to low-dose cabergoline is regularly observed in patients with macroprolactinomas, but the concurrent fall in the plasma ACTH level and hypocortisolism was a pleasant surprise.

We assume that he most likely has a single bihormonal adenoma that is enriched with dopamine-2 receptors.

From http://casereports.bmj.com/content/2017/bcr-2017-219921.short?rss=1

Topical Steroid Use in Psoriasis Patient Leads to Severe Adrenal Insufficiency

This article is written live from the American Association of Clinical Endocrinologists (AACE) 2017 Annual Meeting in Austin, TX. MPR will be reporting news on the latest findings from leading experts in endocrinology. Check back for more news from AACE 2017.

 

At the AACE 2017 Annual Meeting, lead study author Kaitlyn Steffensmeier, MS III, of the Dayton Veterans Affairs (VA) Medical Center, Dayton, OH, presented a case study describing a patient “who developed secondary adrenal insufficiency secondary to long-term topical steroid use and who with decreased topical steroid use recovered.”

The patient was a 63-year-old white male with a 23-year history of psoriasis. For 18 years, the patient had been applying Clobetasol Propionate 0.05% topically on several areas of his body every day. Upon presentation to the endocrine clinic for evaluation of his low serum cortisol, the patient complained of a 24-pound weight gain over a 2-year period, feeling fatigued, as well as facial puffiness.

Laboratory analysis found that the patient’s random serum cortisol and ACTH levels were low (0.2µg/dL and <1.1pg/mL, respectively). According to the study authors, “the labs were indicative of secondary adrenal insufficiency.” Additionally, a pituitary MRI “showed a 2mm hypoenhancing lesion within the midline of the pituitary gland consistent with Rathke’s cleft cyst versus pituitary microadenoma.”

The patient was initiated on 10mg of hydrocortisone in the morning and 5mg in the evening and was instructed to decrease the use of his topical steroid to one time per month. For the treatment of his psoriasis, the patient was started on apremilast, a phosphodiesterase-4 enzyme (PDE4) inhibitor, and phototherapy.

After 2.5 years, the patient had a subnormal response to the cosyntropin stimulation test. However, after 3 years, a normal response with an increase in serum cortisol to 18.7µg/dL at 60 minutes was obtained; the patient was then discontinued on hydrocortisone. Additionally, a stable pituitary tumor was shown via a repeat pituitary MRI.

The study authors explained that, although secondary adrenal insufficiency is not commonly reported, “one study showed 40% of patients with abnormal cortisol response to exogenous ACTH after two weeks of topical glucocorticoids usage.” Another meta-analysis of 15 studies (n=320) revealed 4.7% of patients developing adrenal insufficiency after using topical steroids. Because of this, “clinicians need to be aware of potential side effects of prolong topical steroid use,” added the study authors.

For continuous endocrine news coverage from the AACE 2017 Annual Meeting, check back to MPR’s AACE page for the latest updates.

From http://www.empr.com/aace-2017/topical-steroid-psoriasis-clobestasol-propionate/article/654335/

Pituitary Issues: Irregular Periods

Q: I am 28 years old and I have not yet started my periods naturally. I have to take medicine for periods — Novelon. The doctors say that there is some problem with my hormones in the pituitary gland. Please advise me how to get normal and natural periods, because after taking the medicine I get my period, but without medicines I don’t.

A by Dr Sharmaine Mitchell: The problem you have with your menstrual period being irregular is most likely due to overproduction of the hormone prolactin by the pituitary gland in the brain. The pituitary gland can sometimes enlarge and cause an overproduction of prolactin and this can result in inappropriate milk production in the breasts (white nipple discharge), irregular menstruation or absent menstrual periods, headaches and blurred vision. The blurred vision occurs as a result of compression of the optic nerve which supplies the eyes, by the enlarged brain tumour in the pituitary gland.

You should get a magnetic resonance imaging (MRI) or CT scan of the brain and pituitary gland done. You should also test your prolactin levels to determine the extent of overproduction of the hormone.

Other investigations should include a thyroid function test (TSH), follicle stimulating hormone (FSH) and leutinizing hormone (LH), and baseline testosterone level tests.

Abnormalities in the production of thyroid hormones can also cause menstrual irregularities and this should be ruled out.

Polycystic ovarian disease can also cause irregular menstrual periods and checking the level of FSH, LH and testosterone will help to rule out this diagnosis. This condition is usually associated with excessive weight gain, abnormal male pattern distribution on the face, chest and abdomen and an increased risk for diabetes mellitus. A pelvic ultrasound to look at the structure of the ovaries and to rule out polycystic ovaries is essential.

If the pituitary gland is enlarged, then medication can be prescribed to shrink it. Bromocriptine or Norprolac are commonly used drugs which work well in reducing the prolactin levels and establishing regular menstrual cycles. The use of these drugs will also help to establish ovulation and improve your fertility.

In some cases it may become necessary to have surgery done if the tumour in the pituitary gland is large and does not respond to the usual medications prescribed to shrink the pituitary gland. The MRI of the brain and pituitary gland will give an idea as to the size of the gland and help to determine if there is a need for you to see the neurosurgeon.

In most cases medical management with drugs will work well and there is no need for surgical intervention. This is a problem that can recur, so it may be necessary to take treatment intermittently for a long period of time, especially if fertility is desired.

Consult your doctor who will advise you further. Best wishes.

Dr Sharmaine Mitchell is an obstetrician and gynaecologist. Send questions via e-mail to allwoman@jamaicaobserver.com; write to All Woman, 40-42 1/2 Beechwood Ave, Kingston 5; or fax to 968-2025. All responses are published. Dr Mitchell cannot provide personal responses.

DISCLAIMER:

The contents of this article are for informational purposes only and must not be relied upon as an alternative to medical advice or treatment from your own doctor.

From http://www.jamaicaobserver.com/magazines/allwoman/Still-no-normal-period-at-28_87596

Into the brain through the nostrils (Sri Lanka)

There is purposeful concentration, while soft and soothing music plays in the background, as different teams of doctors and nurses, scrub up and move around Operating Theatre (OT) C of the Anuradhapura Teaching Hospital.

On the operating table is a pretty middle-aged woman, but something seems unusual with her face – it seems unduly large, with the nose being pronounced.

While Consultant Anaesthetist Dr. Ayesha Abeyratne and her team are preparing the patient for surgery, two Consultants from different specialties are studying the Magnetic Resonance Imaging pictures. They are Consultant Ear, Nose and Throat (ENT) Surgeon, Dr. Daminda Dumingoarachchi who is also a Head and Neck Surgeon and Consultant Neurosurgeon, Dr. Stravinsky Perera. Although not present in the OT that day, Consultant ENT Surgeon Dr. Upul Abeysundara is also very much a part of this pioneering work in Sri Lanka.

It is a Monday morning and we too are in OT clothes and masks privy to viewing an operation not done anywhere else in the state sector, except the Anuradhapura Hospital.

Accessing the patient’s brain through the nostrils is what the ENT and Neuro Teams will do in one of many trailblazing procedures, while the Anaesthetic Team will ensure that her vitals are stable and the able theatre nursing staff will play their part.

Image-guided (navigation-assisted) endoscopic trans-nasal trans-sphenoidal pituitary surgery is what we are about to view being performed in the country only since October this year. For, the 38-year-old patient lying inert on the operating table has a tumour just above her pituitary gland, between the optic nerves and the carotid arteries, making it a difficult operation-site to access. (The pea-size pituitary gland is dubbed the ‘master gland’ as it produces many hormones for the whole body, while also stimulating other glands to produce other hormones.)

Dr. Dumingoarachchi points out that the ENT navigator which the Anuradhapura Hospital was provided with recently, is like the GPS system of the brain which shows this vital organ’s architecture.

Dr. Perera explains that the patient has acromegaly, the abnormal production of growth hormones from the pituitary, causing a large nose and big hands etc. This is while it also causes an abnormal reduction in other hormones, affecting the functioning of the whole body. The enlarged pituitary is also compressing the main artery of the brain. A major issue is that the patient’s vision is being affected and if the tumour is not decompressed, she would go blind.

Dr. Daminda Dumingoarachchi

Matters also seem complicated as the patient had undergone ‘conventional’ brain surgery to remove an earlier tumour in the same area in 2009 in another hospital, but some parts had been left behind because it was complex surgery and the slightest slip of the scalpel could cause serious harm.

We watch in fascination as the surgical teams discuss how the tumour has grown around the right carotid artery making it a challenging procedure and is pressing down (compressing) on the brain.

This pituitary macroadenoma with acute intra-tumoural haemorrhage (bleeding) is “big” — 5X3.8X3.5cms, says Dr. Perera, adding that laterally, the lesion extends to the right cavernous sinus encircling almost the full circumference of the cavernous part of the right carotid artery. The left carotid artery is spared.

Super-imposing the patient’s Computed Tomography (CT) scan with images of the real anatomy, the ‘registration’ takes place for this ‘re-do’ surgery, as he explains that the anatomy is distorted after her previous surgery done seven years ago.

In the freezing OT, we don’t feel the time passing as both the Neurosurgeon and the ENT Surgeon attend to their tasks, two pairs of hands working in tandem, not looking down at the patient but up at the two screens, while navigating the pathways through the nostrils to the brain.

Usually, such a large tumour above the pituitary gland will entail open-skull surgery, with the brain having to be retracted (drawn away from the site of the operation) to gain access to the tumour, we learn. While the dangers of such surgery are numerous, the patient also has to spend a long time in the Intensive Care Unit (ICU) in the recovery phase.

With the frontiers of medicine pushed back more and more, Dr. Dumingoarachchi says that now skull-base structures can be approached through the nose, ear and throat. “Such surgery involves dealing with pathologies located on the under-surface of the brain, with Neurosurgeons and ENT Surgeons together accessing the skull-base more easily through the nose, ear and throat.”

Pointing out that these trans-nasal and trans-labyrinthine approaches to the skull-base will help bring down the rate of revision neurosurgeries and cut down the time that the patient will have to spend in the ICU post-operatively, he adds that the patients can go back home sooner without complications and be productive more quickly. Currently, some patients even go to other countries to get these services.

With the Health Ministry providing a high definition 3-chip endoscopic camera system, an anterior skull-base set, a micro-debrider and an ENT navigator, vast strides have been made at the Anuradhapura Hospital. They include:

Dr. Stravinsky Perera

Anterior skull-base surgeries — Endoscopic anterior skull-base surgeries, starting with pituitary surgeries using the endoscopic trans-sphenoidal approach for the first time in Sri Lanka. The latest addition, in October this year, is image-guidance (navigation).

The other procedures include cranio-pharyngioma, olfactory neuroblastoma, cerebrospinal fluid leak repairs, para-nasal sinus cancer resections and odontoid (cervical spine) decompression.

The advantages of this approach include a better field of view and ease of doing revision surgery if required, while leaving no external scars.

Nasal polyposis is also now being managed by image-guided powered full house functional endoscopic sinus surgeries, resulting in the reduction of the recurrence rate. This also cuts down revision surgeries.

*  Lateral skull-base surgeries – Through microscopic lateral skull-base surgery, trans-labyrinthine acoustic neuromas have been removed. With direct access to these eighth-nerve tumours, no brain retraction has been necessitated, resulting in less post-operative morbidity. The whole tumour can be removed while preserving the seventh cranial nerve, as the hospital has also been given intra-operative cranial nerve monitoring facilities.

Paying tribute to Dr. Palitha Mahipala, Director-General of Health Services, for making the navigator available to them, Dr. Dumingoarachchi also expresses appreciation to the Deputy Director-General (DDG) of the Biomedical Division, Muditha Jayathilake, Biomedical Engineers Apsara and Kumuduni and DDG Dr. Lakshmi Somatunga for all their support.

From http://www.sundaytimes.lk/161218/news/into-the-brain-through-the-nostrils-221019.html

Day 18, Cushing’s Awareness Challenge 2016

I have seen this image several places online and it never ceases to crack me up. Sometimes, we really have strange things going on inside our bodies.

Usually, unlike Kermit, we ourselves know that something isn’t quite right, even before the doctors know. Keep in touch with your own body so you’ll know, even before the MRI.

I asked doctors for several years – PCP, gynecologist, neurologist, podiatrist – all said the now-famous refrain. “It’s too rare. You couldn’t have Cushing’s.” I kept persisting in my reading, making copies of library texts even when I didn’t understand them, keeping notes. I just knew that someone, somewhere would “discover” that I had Cushing’s.

Finally, someone did.

These days, there’s no excuse to keep you from learning all you can about what’s going on with you. There’s your computer and the internet. Keep reading and learning all you can. You have a vested interest in what’s going on inside, not your doctor.