Crinetics Pharmaceuticals (CRNX) Reports Positive Top-line Results Including Strong Adrenal Suppression from CRN04894 Phase 1 Study

Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced positive results from the multiple-ascending dose (MAD) portion of a first-in-human Phase 1 clinical study of CRN04894, the company’s first-in-class, investigational, oral, nonpeptide adrenocorticotropic hormone (ACTH) antagonist that is being developed for the treatment of Cushing’s disease, congenital adrenal hyperplasia (CAH) and other conditions of excess ACTH. Following administration of CRN04894, results showed serum cortisol below normal levels and a marked reduction in 24-hour urine free cortisol excretion in the presence of sustained, disease-like ACTH concentrations.

“The design of our Phase 1 healthy volunteer study allowed us to demonstrate CRN04894’s potent pharmacologic activity in the presence of ACTH levels that were in similar range to those seen in CAH and Cushing’s disease patients,” said Alan Krasner, M.D., Crinetics’ chief medical officer. “The observation of dose-dependent reductions in serum cortisol levels to below the normal range even in the presence of high ACTH indicates that CRN04894 was effective in blocking the key receptor responsible for regulating cortisol secretion. We believe this is an important finding that may be predictive of CRN04894’s efficacy in patients.”

ACTH is the key regulator of the hypothalamic-pituitary adrenal (HPA) axis controlling adrenal activation. It is regulated by cortisol via a negative feedback loop that acts to inhibit ACTH secretion. This feedback loop is dysregulated in diseases of excess ACTH. In Cushing’s disease, a benign pituitary tumor drives excess ACTH secretion even in the presence of excess cortisol. While in CAH, an enzyme deficiency results in excess androgen synthesis without normal cortisol synthesis, allowing unchecked ACTH production and requiring lifelong glucocorticoid use. In both diseases, excess ACTH drives over-stimulation of the adrenal gland and leads to a host of symptoms including infertility, adrenal rest tumors, and metabolic complications in CAH and, in Cushing’s disease, symptoms include hypertension, central obesity, neuropsychiatric disorders and metabolic complications. To our knowledge, no other ACTH antagonists are currently in clinical development for diseases of ACTH excess such as Cushing’s disease or CAH.

The 49 healthy adults evaluated in the multiple ascending dose portion of the Phase 1 study were administered 40, 60 or 80 mg doses of CRN04894, or placebo, daily for 10 days. After 10 days of dosing was complete, evaluable participants were administered an ACTH challenge to stimulate adrenal activation to disease relevant levels. Safety and pharmacokinetic data were consistent with expectations from the single-ascending dose cohorts in the Phase 1 study. There were no discontinuations due to treatment-related adverse events and no serious adverse events reported. Glucocorticoid deficiency was the most common treatment-related adverse event in the MAD cohorts. This was an expected extension of pharmacology given the mechanism of action of CRN04894. CRN04894 showed consistent oral bioavailability in the MAD cohorts with a half-life of approximately 24 hours, which is anticipated to support once-daily dosing.

Participants in the MAD cohorts who were administered once nightly CRN04894 experienced a dose-dependent suppression of adrenal function as measured by suppression of serum cortisol production of 17%, 29% and 37% on average from baseline over 24 hours for the 40, 60 or 80 mg dosing groups respectively, (despite requirement for glucocorticoid supplementation in some of these subjects to prevent clinical adrenal insufficiency), compared to an average 2% increase in serum cortisol for individuals receiving placebo. The strong, dose-dependent suppression of serum and urine free cortisol was achieved despite ACTH levels in subjects in the 60 and 80 mg cohorts similar to those typically seen in patients with CAH and Cushing’s disease. Even when an additional exogenous ACTH challenge was administered on top of the already increased ACTH levels, cortisol levels remained below the normal range in subjects receiving CRN04894, indicating clinically significant suppression of adrenal activity.

“Due to its central position in HPA axis, ACTH is the obvious target for inhibiting excessive stimulation of the adrenal in diseases of ACTH excess. Even though the field of endocrinology has known about its clinical significance for more than 100 years, we are not aware of any other ACTH antagonist that has entered clinical development. This is an important milestone for endocrinology and for our company.” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “We are very excited to initiate patient studies in Cushing’s disease and CAH with CRN04894, which will be our third home-grown NCE to demonstrate pharmacologic proof-of-concept and enter patient trials.”

Crinetics plans to present additional details of safety, efficacy, and biomarker results from the CRN04894 Phase 1 study at an endocrinology-focused medical meeting in 2022.

Data Review Conference Call Crinetics will hold a conference call and live audio webcast today, May 25, 2022, at 8:00 a.m. Eastern Time to discuss results from the MAD cohorts of the Phase 1 study of CRN04894. To participate, please dial 1-877-407-0789 (domestic) or 1-201-689-8562 (international) and refer to conference ID 13730000. To access the webcast, click here. Following the live event, a replay will be available on the Events page of the Company’s website.

About the CRN04894 Phase 1 Study Crinetics has completed enrollment of the 88 healthy volunteers in this double-blind, randomized, placebo-controlled Phase 1 study. Participants were divided into multiple cohorts in the single ascending dose (n=39) and multiple ascending dose (n=49) portions of the study. In both the SAD and MAD portions of the study, safety and pharmacokinetics were assessed. In addition, pharmacodynamic responses were evaluated before and after challenges with injected synthetic ACTH to assess pharmacologic effects resulting from exposure to CRN04894.

From https://www.streetinsider.com/Corporate+News/Crinetics+Pharmaceuticals+(CRNX)+Reports+Positive+Top-line+Results+Including+Strong+Adrenal+Suppression+from+CRN04894+Phase+1+Study/20126484.html

Levoketoconazole improves cortisol control in endogenous Cushing’s syndrome

Compared with placebo, levoketoconazole improved cortisol control and serum cholesterol levels for adults with endogenous Cushing’s syndrome, according to results from the LOGICS study presented here.

Safety and efficacy of levoketoconazole (Recorlev, Xeris Biopharma) for treatment of Cushing’s syndrome were established in the pivotal phase 3, open-label SONICS study. The phase 3, double-blind LOGICS study sought to demonstrate the drug specificity of levoketoconazole in normalizing mean urinary free cortisol (mUFC) level.

“Treatment with levoketoconazole benefited patients with Cushing’s syndrome of different etiologies and a wide range in UFC elevations at baseline by frequent normalization of UFC,” Ilan Shimon, MD, professor at the Sackler Faculty of Medicine at Tel Aviv University and associate dean of the Faculty of Medicine at Rabin Medical Center and director of the Institute of Endocrinology in Israel, told Healio. “This is a valuable Cushing’s study as it includes a placebo-controlled randomized withdrawal phase.”

LOGICS participants were drawn from a cohort of 79 adults with Cushing’s syndrome with a baseline mUFC at least 1.5 times the upper limit of normal who participated in a single-arm, open-label titration and maintenance phase of approximately 14 to 19 weeks. Researchers randomly assigned 39 of those participants plus five from SONICS who had normalized mUFC levels on stable doses of levoketoconazole for at least 4 weeks to continue to receive the medication (n = 22) or to receive placebo with withdrawal of the medication (n = 22) for 8 weeks. At the end of the withdrawal period, all participants received levoketoconazole for 8 more weeks. Primary endpoint was proportion of participants who lost mUFC normalization during the randomized withdrawal period, and secondary endpoints included proportion with normalized mUFC and changes in total and LDL cholesterol at the end of the restoration period.

During the withdrawal period, 95.5% of participants receiving placebo vs. 40.9% of those receiving levoketoconazole experienced loss of mUFC response, for a treatment difference of –54.5% (95% CI, –75.7 to –27.4; P = .0002). At the end of the withdrawal period, 4.5% of participants receiving placebo vs. 50% of those receiving levoketoconazole maintained normalized mUFC, for a treatment difference of 45.5% (95% CI, 19.2-67.9; P = .0015).

Among participants who had received placebo and lost mUFC response, 60% regained normalized mUFC at the end of the restoration period.

During the withdrawal period, participants in the placebo group had increases of 0.9 mmol/L in total cholesterol and 0.6 mmol/L in LDL cholesterol vs. decreases of 0.04 mmol/L (P = .0004) and 0.006 mmol/L (P = .0056), respectively, for the levoketoconazole group. The increases seen in the placebo group were reversed when participants restarted the medication.

The most common adverse events with levoketoconazole were nausea (29%) and hypokalemia (26%). Prespecified adverse events of special interest were liver-related (10.7%), QT interval prolongation (10.7%) and adrenal insufficiency (9.5%).

“This study has led to the FDA decision to approve levoketoconazole for the treatment of Cushing’s syndrome after surgical failure or if surgery is not possible,” Shimon said.

From https://www.healio.com/news/endocrinology/20220512/logics-levoketoconazole-improves-cortisol-control-in-endogenous-cushings-syndrome

What Do *You* Think? Smartwatch Measures Cortisone

Share your thoughts here.

The human body responds to stress, from the everyday to the extreme, by producing a hormone called cortisol.

To date, it has been impractical to measure cortisol as a way to potentially identify conditions such as depression and post-traumatic stress, in which levels of the hormone are elevated. Cortisol levels traditionally have been evaluated through blood samples by professional labs, and while those measurements can be useful for diagnosing certain diseases, they fail to capture changes in cortisol levels over time.

Now, a UCLA research team has developed a device that could be a major step forward: A smartwatch that assesses cortisol levels found in sweat—accurately, noninvasively and in real time. Described in a study published in Science Advances, the technology could offer wearers the ability to read and react to an essential biochemical indicator of stress.

“I anticipate that the ability to monitor variations in cortisol closely across time will be very instructive for people with psychiatric disorders,” said co-corresponding author Anne Andrews, a UCLA professor of psychiatry and biobehavioral sciences, member of the California NanoSystems Institute at UCLA and member of the Semel Institute for Neuroscience and Human Behavior. “They may be able to see something coming or monitor changes in their own personal patterns.”

Cortisol is well-suited for measurement through sweat, according to co-corresponding author Sam Emaminejad, an associate professor of electrical and computer engineering at the UCLA Samueli School of Engineering, and a member of CNSI.

“We determined that by tracking cortisol in sweat, we would be able to monitor such changes in a wearable format, as we have shown before for other small molecules such as metabolites and pharmaceuticals,” he said. “Because of its small molecular size, cortisol diffuses in sweat with concentration levels that closely reflect its circulating levels.”

The technology capitalizes on previous advances in wearable bioelectronics and biosensing transistors made by Emaminejad, Andrews and their research teams.

In the new smartwatch, a strip of specialized thin adhesive film collects tiny volumes of sweat, measurable in millionths of a liter. An attached sensor detects cortisol using engineered strands of DNA, called aptamers, which are designed so that a cortisol molecule will fit into each aptamer like a key fits a lock. When cortisol attaches, the aptamer changes shape in a way that alters electric fields at the surface of a transistor.

The invention—along with a 2021 study that demonstrated the ability to measure key chemicals in the brain using probes—is the culmination of a long scientific quest for Andrews. Over more than 20 years, she has spearheaded efforts to monitor molecules such as serotonin, a chemical messenger in the brain tied to mood regulation, in living things, despite transistors’ vulnerability to wet, salty biological environments.

Sweating the small stuff: Smartwatch developed at UCLA measures key stress hormone
The technology capitalizes on previous work by Sam Emaminejad, Anne Andrews and their UCLA research teams. Credit: Emaminejad Lab and Andrews Lab/UCLA

In 1999, she proposed using nucleic acids—rather than proteins, the standard mechanism—to recognize specific molecules.

“That strategy led us to crack a fundamental physics problem: how to make transistors work for electronic measurements in biological fluids,” said Andrews, who is also a professor of chemistry and biochemistry.

Meanwhile, Emaminejad has had a vision of ubiquitous personal health monitoring. His lab is pioneering wearable devices with biosensors that track the levels of certain molecules that are related to specific health measures.

“We’re entering the era of point-of-person monitoring, where instead of going to a doctor to get checked out, the doctor is basically always with us,” he said. “The data are collected, analyzed and provided right on the body, giving us real-time feedback to improve our health and well-being.”

Emaminejad’s lab had previously demonstrated that a disposable version of the specialized adhesive film enables smartwatches to analyze chemicals from sweat, as well as a technology that prompts small amounts of sweat even when the wearer is still. Earlier studies showed that sensors developed by Emaminejad’s group could be useful for diagnosing diseases such as cystic fibrosis and for personalizing drug dosages.

One challenge in using cortisol levels to diagnose depression and other disorders is that levels of the hormone can vary widely from person to person—so doctors can’t learn very much from any single measurement. But the authors foresee that tracking individual cortisol levels over time using the smartwatch may alert wearers, and their physicians, to changes that could be clinically significant for diagnosis or monitoring the effects of treatment.

Among the study’s other authors is Janet Tomiyama, a UCLA associate professor of psychology, who has collaborated with Emaminejad’s lab over the years to test his wearable devices in clinical settings.

“This work turned into an important paper by drawing together disparate parts of UCLA,” said Paul Weiss, a UCLA distinguished professor of chemistry and biochemistry and of materials science and engineering, a member of CNSI, and a co-author of the paper. “It comes from us being close in proximity, not having ego problems and being excited about working together. We can solve each other’s problems and take this technology in new directions.”

The paper’s co-first authors are UCLA postdoctoral scholar Bo Wang and Chuanzhen Zhao, a former UCLA graduate student. Other co-authors are Zhaoqing Wang, Xuanbing Cheng, Wenfei Liu, Wenzhuo Yu, Shuyu Lin, Yichao Zhao, Kevin Cheung and Haisong Lin, all of UCLA; and Milan Stojanović and Kyung-Ae Yang of Columbia University.

From https://techxplore.com/news/2022-02-small-newly-smartwatch-key-stress.html

Synergistic Cortisol Suppression by Ketoconazole–Osilodrostat Combination Therapy

Abstract

Summary

Here, we describe a case of a patient presenting with adrenocorticotrophic hormone-independent Cushing’s syndrome in a context of primary bilateral macronodular adrenocortical hyperplasia. While initial levels of cortisol were not very high, we could not manage to control hypercortisolism with ketoconazole monotherapy, and could not increase the dose due to side effects. The same result was observed with another steroidogenesis inhibitor, osilodrostat. The patient was finally successfully treated with a well-tolerated synergitic combination of ketoconazole and osilodrostat. We believe this case provides timely and original insights to physicians, who should be aware that this strategy could be considered for any patients with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.

Learning points

  • Ketoconazole–osilodrostat combination therapy appears to be a safe, efficient and well-tolerated strategy to supress cortisol levels in Cushing syndrome.
  • Ketoconazole and osilodrostat appear to act in a synergistic manner.
  • This strategy could be considered for any patient with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.
  • Considering the current cost of newly-released drugs, such a strategy could lower the financial costs for patients and/or society.
Keywords: Adult; Male; White; France; Adrenal; Adrenal; Novel treatment; December; 2021

Background

Untreated or inadequately treated Cushing’s syndrome (CS) is a morbid condition leading to numerous complications. The latter ultimately results in an increased mortality that is mainly due to cardiovascular events and infections. The goal of the treatment with steroidogenesis inhibitors is normalization of cortisol production allowing the improvement of comorbidities (1). Most studies dealing with currently available steroidogenesis inhibitors used as monotherapy reported an overall antisecretory efficacy of roughly 50% in CS. Steroidogenesis inhibitors can be combined to better control hypercortisolism. To the best of our knowledge, we report here for the first time a patient treated with a ketoconazole–osilodrostat combination therapy.

Case presentation

Here, we report the case of Mr D.M., 53-years old, diagnosed with adrenocorticotrophic hormone (ACTH)-independent CS 6 months earlier. At diagnosis, he presented with resistant hypertension, hypokalemia, diabetes mellitus, easy bruising, purple abdominal striae and major oedema of the lower limbs.

Investigations

A biological assessment was performed, and the serum cortisol levels are depicted in Table 1. ACTH levels were suppressed (mean levels 1 pg/mL). Mean late-night salivary cortisol showed a four-fold increase (Table 2), and mean 24 h-urinary cortisol showed a two-fold increase. Serum cortisol was 1000 nmol/L at 08:00 h after 1 mg dexamethasone dose at 23:00 h. The rest of the adrenal hormonal workup was within normal ranges (aldosterone: 275 pmol/L and renin: 15 mIU/L). An adrenal CT was performed (Fig. 1) and exhibited a 70-mm left adrenal mass (spontaneous density: 5 HU and relative washout: 65%) and a 45-mm right adrenal mass (spontaneous density: −2 HU and relative washout: 75%). The case was discussed in a multidisciplinary team meeting, which advised to perform 18F-FDG PET-CT and 123I-Iodocholesterol scintigraphy before considering surgery. A genetic screening was performed, testing for ARMC5 and PRKAR1A pathogenic variants.

Figure 1View Full Size
Figure 1
Adrenal CT depicting the bilateral macronodular adrenocortical hyperplasia.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2021, 1; 10.1530/EDM-21-0071

Table 1Serum cortisol levels at diagnosis (A), using ketoconazole monotherapy (B), using osilodrostat monotherapy (C) and using osilodrostat–ketoconazole combination therapy (D).

Serum cortisol (nmol/L) 08:00 h 24:00 h 16:00 h 20:00 h 12:00 h 16:00 h
A. At diagnosis 660 615 716 566 541 561
B. Ketoconazole monotherapy 741 545 502 224 242 508
C. Osilodrostat monotherapy 658 637 588 672 486 692
D. Osilodrostat–ketoconazole combination 436 172 154 103 135 274
Table 2Salivary cortisol levels at diagnosis (A), using ketoconazole monotherapy (B), using osilodrostat monotherapy (C) and using osilodrostat-ketoconazole combination therapy (D).

Salivary cortisol (nmol/L) 23:00 h 12:00 h 13:00 h Mean
A. At diagnosis 47 62 38 49
B. Ketoconazole monotherapy 20 15 21 18
C. Osilodrostat monotherapy 85 90 56 77
D. Osilodrostat–ketoconazole combination 10 14 9 11

Treatment

As this condition occurred during the COVID-19 pandemic, it was decided to first initiate steroidogenesis inhibitors to lower the patient’s cortisol levels. Initially, ketoconazole was initiated and uptitrated up to 1000 mg per day based on close serum cortisol monitoring, with a three-fold increase of liver enzymes and poor control of cortisol levels (Table 1). In the absence of biological efficacy, ketoconazole was replaced by osilodrostat, which was gradually increased up to 30 mg per day (10 mg at 08:00 h and 20 mg at 20:00 h) without reaching normal cortisol levels (Table 1) and with slightly increased blood pressure levels. Considering the lack of efficacy of anticortisolic drugs used as monotherapy, we combined osilodrostat (30 mg per day) to ketoconazole (600 mg per day), that is, at the last maximal tolerated dose as monotherapy of each drug.

Outcome

This combination of steroidogenesis inhibitors achieved a good control in cortisol levels, mimicking a physiological circadian rhythm (Table 1D). The patient did not exhibit any side effect and the control of cortisol levels resulted in a rapid improvement of hypertension, kalemia, diabetes control and disappearance of lower limbs oedema. The patient underwent a 18F-FDG PET-CT that did not exhibit any increased uptake in both adrenal masses and a 123I-Iodocholesterol scintigraphy exhibiting a highly increased uptake in both adrenal masses, predominating in the left adrenal mass (70 mm). Unilateral adrenalectomy of the larger mass was then performed, and as the immediate post-operative serum cortisol level was 50 nmol/L, hydrocortisone was administered at a dose of 30 mg per day, with a stepwise decrease to 10 mg per day over 3 months. Pathological examination exhibited macronodular adrenal hyperplasia with a 70-mm adreno cortical adenoma (WEISS score: 1 and Ki67: 1%). The genetic screening exhibited a c.1908del p.(Phe637Leufs*6) variant of ARMC5 (pathogenic), located in exon 5. The patient has no offspring and is no longer in contact with the rest of his family.

Discussion

The goal of the treatment with steroidogenesis inhibitors is normalization of cortisol production allowing the improvement of comorbidities (1). Most studies dealing with currently available steroidogenesis inhibitors used as monotherapy reported an overall antisecretory efficacy of roughly 50% in CS. This rate of efficacy was probably underestimated in retrospective studies due to the lack of adequate uptitration of the dose; For example, the median dose reported in the French retrospective study on ketoconazole was only 800 mg/day, while 50% of the patients were uncontrolled at the last follow-up (2).

Steroidogenesis inhibitors can be combined to better control hypercortisolism. Up to now, such combinations, mainly ketoconazole and metyrapone, were mainly reported in patients with severe CS (median urinary-free Cortisol (UFC) 30- to 40-fold upper-limit norm (ULN)) and life-threatening comorbidities (3, 4). Normal UFC was reported in up to 86% of these patients treated with high doses of ketoconazole and metyrapone. Expected side effects (such as increased liver enzymes for ketoconazole or worsened hypertension and hypokalemia for metyrapone) were reported in the majority of the patients. The fear of these side effects probably explains the lack of uptitration in previous reports. Combination of steroidogenesis inhibitors has previously been described by Daniel et al. in the largest study reported on the use of metyrapone in CS; 29 patients were treated with metyrapone and ketoconazole or mitotane, including 22 in whom the second drug was added to metyrapone monotherapy because of partial efficacy or adverse effects. The final median metyrapone dose in patients controlled with combination therapy was 1500 mg per day (5).

Combination of adrenal steroidogenesis inhibitors should not be reserved to patients with severe hypercortisolism. In the case shown here, the association was highly effective in terms of secretion, using lower doses than those applied as a single treatment, but without the side effects previously observed with higher doses of each treatment used as a monotherapy. To our knowledge, the association of ketoconazole and osilodrostat had never been reported. Ketoconazole blocks several enzymes of the adrenal steroidogenesis such as CYP11A1, CYP17, CYP11B2 (aldosterone synthase) and CYP11B1 (11-hydroxylase), leading to decreased cortisol and occasionally testosterone concentrations. Though liver enzymes increase is not dose-dependent, it usually happens at doses exceeding 400–600 mg per day (2). Osilodrostat blocks CYP11B1 and CYP11B2; a combination should thus allow for a complete blockade of these enzymes that are necessary for cortisol secretion. Short-term side effects such as hypokalemia and hypertension are similar to those observed with metyrapone, due to increased levels of the precursor deoxycorticosterone, correlated with the dose of osilodrostat (6). As for our patient, the occurrence of side effects should not lead to immediately switch to another drug, but rather to decrease the dose and add another cortisol-lowering drug. Moreover, considering the current cost of newly-released drugs such a strategy could lower financial costs for patients and/or society.

Another point to take into account is the current COVID-19 pandemic, for which, as recently detailed in experts’ opinion (7), the main aim is to reach eucortisolism, whatever the way. Indeed patients presenting with CS usually also present with comorbidities such as obesity, hypertension, diabetes mellitus and immunodeficiency (8). Surgery, which represents the gold standard strategy in the management of CS (1, 9), might be delayed to reduce the hospital-associated risk of COVID-19, with post-surgical immunodepression and thromboembolic risks (7). Because immunosuppression and thromboembolic diathesis are common CS features (9, 10), during the COVID-19 pandemic, the use of steroidogenesis inhibitors appears of great interest. In these patients, combing steroidogenesis inhibitors at intermediate doses might allow for a rapid control of hypercortisolism without risks of major side effects if a single uptitrated treatment is not sufficient. Obviously, the management of associated comorbidities would also be crucial in this situation (11).

To conclude, we report for the first time a case of CS, in the context of primary bilateral macronodular adrenocortical hyperplasia successfully treated with a well-tolerated combination of ketoconazole and osilodrostat. While initial levels of cortisol were not very high, we could not manage to control hypercortisolism with ketoconazole monotherapy, and could not increase the dose due to side effects. The same result was observed with another steroidogenesis inhibitor, osilodrostat. This strategy could be considered for any patient with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.

Declaration of interest

F C and T B received research grants from Recordati Rare Disease and HRA Pharma Rare Diseases. Frederic Castinetti is on the editorial board of Endocrinology, Diabetes and Metabolism case reports. Frederic Castinetti was not involved in the review or editorial process for this paper, on which he is listed as an author.

Funding

This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Patient consent

Informed written consent has been obtained from the patient for publication of the case report.

Author contribution statement

V A was the patient’s physician involved in the clinical care and collected the data. T B and F C supervised the management of the patient. F C proposed the original idea of this case report. V A drafted the manuscript. F C critically reviewed the manuscript. T B revised the manuscript into its final version.

References

7 Things Your Hair Reveals About Your Health

Your hair can tell you and your doctor if you are stressed, have a nutritional deficiency, thyroid problem, or other health issues. Here are seven key things to look for in your hair.

You probably think about your hair every day: worrying about a bad day, enjoying a good blow-dry, or wondering if you have to try the new style you noticed in your favorite celebrity. But you may be missing the clues your hair reveals about your health. Research shows that changes in the look, texture, or thickness of your hair can be signs of underlying health issues. Here’s how to tell if your hair changes are due to a health condition, genetics, stress, or a nutritional deficiency.

1 Stress (and genes) can cause you to turn gray

Anyone who has observed the hairstyle changes of a President of the Republic from one campaign to another has noticed that stress seems to cause hair to turn white. A mouse study published in the journal Nature suggests that chronic stress may actually contribute to white hair by causing DNA damage and reducing the number of pigment-producing cells in hair follicles. Stress can also lead to hair loss.

Another type of stress, known as oxidative stress, can also play a role in white hair. Oxidative stress can affect pigment-producing cells. Turning gray is actually a completely natural part of aging because hair follicles produce less color as you age. Your genes also play a role in when your hair turns gray. Ask your parents how old they were when they first saw the signs of silvering, and you might do the same. In fact, a study published in March 2016 in the journal Nature Communications was the first to identify the gene responsible for white hair.

2 brittle hair could be a sign of Cushing’s syndrome

Brittle hair is one of the symptoms of Cushing’s syndrome, which is a rare condition caused by excess cortisol, the main hormone body stress. But, there are many other, more obvious symptoms of Cushing’s syndrome, including high blood pressure, fatigue, and back pain. Treatment for Cushing’s syndrome may involve changing the dose of medication that may be causing the condition, such as glucocorticoids, which are steroids used to treat inflammation caused by various diseases.

3 Thinning hair may be a sign of thyroid disease

People with hypothyroidism, a condition that occurs when the thyroid gland does not produce enough thyroid hormones, may notice increased hair loss and change in hair appearance. About 4.6% of the population aged 12 years and older have hypothyroidism, although most cases are mild. Hypothyroidism can lead to thinning hair and other symptoms, such as fatigue, intolerance to cold, joint pain, muscle aches, puffy face and weight gain. A thyroid stimulating hormone (TSH) test can diagnose the condition, and treatment involves taking thyroid medication.

In addition to thinning hair, some thyroid disorders put you at risk for risk of autoimmune hair loss called alopecia areata. This type of hair loss causes round patches of sudden hair loss and is caused by the immune system attacking the hair follicles.

4 Hair loss can be a sign of anemia

If you suddenly notice a lot more hair in your hairbrush or on the floor of your shower, it may be a sign that your body has low iron stores, or anemia , and may warrant testing. This is another blood test we do when you complain of hair changes. Vegetarians or women with heavy periods increase their risk that hair changes are due to iron deficiency.

It is unclear why iron deficiency can lead to hair loss. hair, but iron is essential for many biological and chemical reactions, perhaps including hair growth. Hair loss can also occur (temporarily) with sudden changes in estrogen levels and is often noticed after pregnancy or stopping birth control pills.

5 The loss of hair could indicate protein deficiency

Protein is essential for hair health and growth (a lack of protein has been linked to hair thinning and hair loss ). Protein deficiency is not a problem for most people. Most adults need 0.8 grams of protein per kilogram of body weight. Good sources of protein include low-fat Greek yogurt, chickpeas, and chicken breast. People who have gastrointestinal difficulties or who have just had gastric bypass surgery may have problems digesting protein. These special situations will need to be managed with the help of your doctor. But most cases of thinning hair, even in women, are probably due to genetics.

6 White or yellow flakes can mean you have dandruff

Yellow or white flakes in your hair, on your shoulders and even in your eyebrows are a sign of dandruff, a chronic scalp condition. Dandruff is usually not a sign of a health problem and can be treated with specialized over-the-counter or prescription shampoos.

One of the most common causes of dandruff is a medical condition called seborrheic dermatitis. People with seborrheic dermatitis have red, oily skin covered in white or yellow scales. A yeast-like fungus called malassezia can also irritate the scalp. Insufficient shampoo, sensitivity to hair care products, and dry skin can also cause dandruff. (Dandruff is usually more severe in the winter, when indoor heating can make skin drier).

7 Damaged hair can mask other health issues

Although hair can reveal your condition, women more often complain about the damage caused by hair coloring and heat treatment. Excessive heat, from daily use of a flat iron or blow-drying, can certainly damage your hair, making it dry, brittle and difficult to maintain. Best not to use more than one hot tool per day (occasional double heat treatment is okay, but not daily). When applying heat to your hair, always use products with protective ingredients. Serums and shine drops tend to have hair-preserving qualities when using direct and indirect heat.

From https://www.mvdemocrat.com/appearance-texture-thickness-7-things-your-hair-reveals-about-your-health/

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